The Experts below are selected from a list of 2553 Experts worldwide ranked by ideXlab platform

Jeffrey B Rosen - One of the best experts on this subject based on the ideXlab platform.

  • Corticotropin releasing factor type-1 receptor antagonism in the dorsolateral bed nucleus of the stria terminalis disrupts contextually conditioned fear, but not unconditioned fear to a Predator Odor
    Psychoneuroendocrinology, 2016
    Co-Authors: Arun Asok, Jay Schulkin, Jeffrey B Rosen
    Abstract:

    The bed nucleus of the stria terminalis (BNST) plays a critical role in fear and anxiety. The BNST is important for contextual fear learning, but the mechanisms regulating this function remain unclear. One candidate mechanism is corticotropin-releasing-factor (CRF) acting at CRF type 1 receptors (CRFr1s). Yet, there has been little progress in elucidating if CRFr1s in the BNST are involved in different types of fear (conditioned and/or unconditioned). Therefore, the present study investigated the effect of antalarmin, a potent CRFr1 receptor antagonist, injected intracerebroventricularly (ICV) and into the dorsolateral BNST (LBNST) during single trial contextual fear conditioning or exposure to the Predator Odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). Neither ICV nor LBNST antalarmin disrupted unconditioned freezing to TMT. In contrast, ICV and LBNST antalarmin disrupted the retention of contextual fear when tested 24h later. Neither ICV nor LBNST antalarmin affected baseline or post-shock freezing-indicating antalarmin does not interfere with the early phases of contextual fear acquisition. Antalarmin did not (1) permanently affect the ability to learn and express contextual fear, (2) change responsivity to footshocks, or (3) affect the ability to freeze. Our findings highlight an important role for CRFr1s within the LBNST during contextually conditioned fear, but not unconditioned Predator Odor fear.

  • Changes in dam and pup behavior following repeated postnatal exposure to a Predator Odor (TMT): A preliminary investigation in Long-Evans rats.
    Developmental psychobiology, 2015
    Co-Authors: Luke W. Ayers, Arun Asok, Jennifer Blaze, Tania L. Roth, Jeffrey B Rosen
    Abstract:

    The present study investigated whether repeated early postnatal exposure to the Predator Odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) alters behavioral responses to the stimulus later in life, at postnatal day (PN30). Long-Evans rat pups with their mothers were exposed for 20 min daily to TMT, water, or a noxious Odor, butyric acid (BTA), during the first three weeks of life. Mothers exposed to TMT displayed more crouching and nursing behavior than those exposed to BTA, and TMT exposed pups emitted more ultrasonic vocalizations than BTA exposed pups. At PN30, rats were tested for freezing to TMT, water, or BTA. Rats exposed to TMT during the postnatal period displayed less freezing to TMT than rats exposed postnatally to water or BTA. Our data indicate that early-life experience with a Predator cue has a significant impact on later fear responses to that same cue, highlighting the programming capacity of the postnatal environment on the development of behavior.

  • The smell of fear: innate threat of 2,5-dihydro-2,4,5-trimethylthiazoline, a single molecule component of a Predator Odor.
    Frontiers in neuroscience, 2015
    Co-Authors: Jeffrey B Rosen, Arun Asok, Trisha Chakraborty
    Abstract:

    In the last several years, the importance of understanding what innate threat and fear is, in addition to learning of threat and fear, has become evident. Odors from Predators are ecologically relevant stimuli used by prey animals as warnings for the presence of danger. Of importance, these Odors are not necessarily noxious or painful, but they have innate threat-like properties. This review summarizes the progress made on the behavioral and neuroanatomical fundamentals of innate fear of the Predator Odor, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a component of fox feces. TMT is one of several single molecule components of Predator Odors that have been isolated in the last several years. Isolation of these single molecules has allowed for rapid advances in delineating the behavioral constraints and selective neuroanatomical pathways of Predator Odor induced fear. In naive mice and rats, TMT induces a number of fear and defensive behaviors, including robust freezing, indicating it is an innate threat stimulus. However, there are a number of behavioral constraints that we do not yet understand. Similarly, while some of the early olfactory sensory pathways for TMT-induced fear are being delineated, the pathways from olfactory systems to emotional and motor output regions are less well understood. This review will focus on what we know and what we still need to learn about the behavior and neuroanatomy of TMT-induced fear.

  • Freezing to the Predator Odor 2,4,5 dihydro 2,5 trimethylthiazoline (TMT) is disrupted by olfactory bulb removal but not trigeminal deafferentation.
    Behavioural brain research, 2013
    Co-Authors: Luke W. Ayers, Arun Asok, Frankie D. Heyward, Jeffrey B Rosen
    Abstract:

    Abstract 2,4,5 dihydro 2,5 trimethylthiazoline (TMT) is a synthesized component of red fox anal secretions that reliably elicits defensive behaviors in rats and mice. TMT differs from other Predator Odors because it is a single molecule, it can be synthesized in large quantities, and the dose for exposure is highly controllable in an experimental setting. TMT has become a popular tool for studying the brain mechanisms that mediate innate fear behavior to olfactory stimuli. However, this view of TMT as a biologically relevant olfactory stimulus has been challenged by suggestions that the Odor elicits fear behavior due to its irritating properties, presumably working through a nociceptive mechanism. To address this criticism our lab measured freezing behavior in rats during exposures to 2 Odors (TMT and butyric acid) and H 2 O (no Odor control) following either surgical transection of the trigeminal nerves or ablation of the olfactory bulbs. Our findings (Experiment 1) indicate that freezing behavior to TMT requires an intact olfactory system, as indicated by the loss of freezing following olfactory bulb removal. Experiment 2 revealed that rats with trigeminal nerve transection freeze normally to TMT, suggesting the olfactory system mediates this behavior to TMT. A replication of Experiment 1 that included contextual fear conditioning revealed that the decreased freezing behavior was not due to an inability of olfactory bulb ablated rats to freeze (Experiment 3). Taken together, these findings support TMT's role as an ecologically relevant Predator Odor useful in experiments of unconditioned fear that is mediated via olfaction and not nociception.

  • Immediate early gene and neuropeptide expression following exposure to the Predator Odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT).
    Behavioural brain research, 2013
    Co-Authors: Arun Asok, Luke W. Ayers, Bisola Awoyemi, Jay Schulkin, Jeffrey B Rosen
    Abstract:

    a b s t r a c t The immediate early gene c-fos and a number of neuropeptides have been widely used to help delineate the neural circuitry of innate fear to Predator Odors. The present study used in situ hybridization tech- niques to examine the expression of the immediate early gene transcription factors c-fos and egr-1, and the neuropeptides corticotropin-releasing hormone (crh) and enkephalin (enk) following exposure to the Predator Odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). Rats were exposed to water (H2O), TMT, or the irritating Odor butyric acid (BA) and freezing was used to measure fear behavior. Changes in gene expression were analyzed in the medial prefrontal cortex (mPFC), the bed nucleus of the stria terminalis (BNST), paraventricular nucleus of the hypothalamus (PVN), and central nucleus of the amygdala (CeA). Animals froze more to TMT than BA and H2O, and more to BA than H2O. Compared to H2O and BA, c-fos and egr-1 were elevated within the BNST, PVN, and CeA in rats exposed to TMT, but not the mPFC. Crh was also elevated in rats exposed to TMT within the CeA and PVN, but not the BNST or mPFC. Enk was elevated within the PVN in TMT and BA exposed rats compared to H2O exposure. These data indicate that exposure to the Predator Odor TMT induces similar expression patterns for c-fos and egr-1, but different patterns for crh and enk, with partial overlap of the immediate-early genes and neuropeptides within specific brain regions. © 2013 Elsevier B.V. All rights reserved.

Nicholas W. Gilpin - One of the best experts on this subject based on the ideXlab platform.

  • The role of central amygdala corticotropin-releasing factor in Predator Odor stress-induced avoidance behavior and escalated alcohol drinking in rats.
    Neuropharmacology, 2020
    Co-Authors: Marcus M. Weera, Allyson L. Schreiber, Elizabeth M. Avegno, Nicholas W. Gilpin
    Abstract:

    Abstract Post-traumatic stress disorder (PTSD) is characterized by avoidance of trauma-associated stimuli and amygdala hyperreactivity, and is highly co-morbid with alcohol use disorder (AUD). Our lab uses a Predator Odor (bobcat urine) stress model that produces conditioned avoidance of an Odor-paired context in a subset of rats, mirroring avoidance symptoms that manifest in some but not all humans exposed to trauma. We previously showed that after Predator Odor stress, Avoiders exhibit escalated operant alcohol self-administration (SA), higher aversion-resistant operant alcohol responding, hyperalgesia, and greater anxiety-like behavior compared to unstressed Controls. We also showed previously that systemic antagonism of corticotropin-releasing factor-1 receptors (CRFR1) reduced escalation of operant alcohol SA in rats not indexed for avoidance, that corticotropin-releasing factor (CRF) infusions into the central amygdala (CeA) produced conditioned place avoidance in stress-naive rats, and that intra-CeA infusion of a CRFR1 antagonist reduced hyperalgesia in Avoiders. Here, we show that avoidance behavior is persistent after repeated Predator Odor exposure. In addition, Avoiders showed lower weight gain than Controls after Predator Odor re-exposure. In the brain, higher avoidance was correlated with higher number of c-Fos + cells and CRF immunoreactivity in the CeA. Finally, we show that intra-CeA CRFR1 antagonism reversed post-stress escalation of alcohol SA and reduced avoidance behavior in Avoiders. Collectively, these findings suggest that elucidation of the mechanisms by which CRFR1-gated CeA circuits regulate avoidance behavior and alcohol SA may lead to better understanding of the neural mechanisms underlying co-morbid PTSD and AUD.

  • The Role of Central Amygdala Corticotropin-Releasing Factor in Predator Odor Stress-Induced Avoidance Behavior and Escalated Alcohol Drinking in Rats
    2019
    Co-Authors: Marcus M. Weera, Allyson L. Schreiber, Elizabeth M. Avegno, Nicholas W. Gilpin
    Abstract:

    ABSTRACT Post-traumatic stress disorder (PTSD) is characterized by avoidance of trauma-associated stimuli and amygdala hyperreactivity, and is highly co-morbid with alcohol use disorder (AUD). Our lab uses a Predator Odor (bobcat urine) stress model that produces conditioned avoidance of an Odor-paired context in a subset of rats, mirroring avoidance symptoms that manifest in some but not all humans exposed to trauma. We previously showed that after Predator Odor stress, Avoiders exhibit escalated alcohol drinking, higher aversion-resistant operant alcohol responding, hyperalgesia, and greater anxiety-like behavior compared to unstressed Controls. We also showed that systemic antagonism of corticotropin-releasing factor-1 receptors (CRFR1) reduced escalation of alcohol drinking in rats not indexed for avoidance, that corticotropin-releasing factor (CRF) infusions into the central amygdala (CeA) produced conditioned place avoidance in stress-naive rats, and that intra-CeA infusion of a CRFR1 antagonist reduced hyperalgesia in Avoiders. Here, we show that avoidance behavior is persistent after repeated Predator Odor exposure and is resistant to extinction. In addition, Avoiders showed lower weight gain than Controls after Predator Odor re-exposure. In the brain, higher avoidance was correlated with higher number of c-Fos+ cells and CRF immunoreactivity in the CeA. Finally, we show that intra-CeA CRFR1 antagonism reversed post-stress escalation of alcohol drinking and reduced avoidance behavior in Avoiders. Collectively, these findings suggest that elucidation of the mechanisms by which CRFR1-gated CeA circuits regulate avoidance behavior and alcohol drinking may lead to better understanding of the neural mechanisms underlying co-morbid PTSD and AUD.

  • The Predator Odor avoidance model of post-traumatic stress disorder in rats.
    Behavioural pharmacology, 2019
    Co-Authors: Lucas Albrechet-souza, Nicholas W. Gilpin
    Abstract:

    Individuals with post-traumatic stress disorder avoid trauma-related stimuli and exhibit blunted hypothalamic-pituitary-adrenal axis response at the time of trauma. Our laboratory uses Predator Odor (i.e. bobcat urine) stress to divide adult Wistar rats into groups that exhibit high (avoiders) or low (nonavoiders) avoidance of a Predator Odor-paired context, modeling the fact that not all humans exposed to traumatic events develop psychiatric conditions. Male avoiders exhibit lower body weight gain after stress, as well as extinction-resistant avoidance that persists after a second stress exposure. These animals also show attenuated hypothalamic-pituitary-adrenal axis response to Predator Odor that predicts subsequent avoidance of the Odor-paired context. Avoiders exhibit unique brain activation profiles relative to nonavoiders and controls (as measured by Fos immunoreactivity), and higher corticotropin-releasing factor levels in multiple brain regions. Furthermore, avoider rats exhibit escalated and compulsive-like alcohol self-administration after traumatic stress. Here, we review the Predator Odor avoidance model of post-traumatic stress disorder and its utility for tracking behavior and measuring biological outcomes predicted by avoidance. The major strengths of this model are (i) etiological validity with exposure to a single intense stressor, (ii) established approach distinguishing individual differences in stress reactivity, and (iii) robust behavioral and biological phenotypes during and after trauma.

  • Predator Odor stress blunts alcohol conditioned aversion.
    Neuropharmacology, 2018
    Co-Authors: Allyson L. Schreiber, M. Adrienne Mcginn, Scott Edwards, Nicholas W. Gilpin
    Abstract:

    Abstract Alcohol use disorder is highly co-morbid with traumatic stress disorders in humans, and dually diagnosed individuals cite negative affective symptoms as a primary reason for drinking alcohol. Therefore, it is reasonable to hypothesize that traumatic stress history increases the rewarding properties and/or blunts the aversive properties of alcohol. We used a place conditioning procedure to test the rewarding/aversive properties of alcohol in adult male Wistar rats with or without a traumatic stress (i.e., Predator Odor exposure) history, and with or without an alcohol drinking history. Because extended amygdala regions have documented roles in stress, reward, and stress-induced changes in reward, we also tested the effect of acute alcohol on CREB phosphorylation (pCREB) and striatal-enriched protein tyrosine phosphatase (STEP) expression in central amygdala (CeA) and bed nucleus of stria terminalis (BNST). Our results show that a moderate alcohol dose (1.0 g/kg) produces conditioned place aversion (CPA) that is blunted by stress history but is not affected by alcohol drinking history, and this effect differed in pair-housed versus single-housed rats. Stress history reduced pCREB expression in BNST of rats with and without an alcohol drinking history. Finally, acute alcohol effects on pCREB and STEP expression in CeA were positively associated with preference for the alcohol-paired chamber. These data suggest that stress history reduces the aversive properties of moderate alcohol doses, and that alcohol aversion is associated with acute alcohol effects on pCREB and STEP expression in the extended amygdala.

  • Blunted hypothalamo-pituitary adrenal axis response to Predator Odor predicts high stress reactivity.
    Physiology & behavior, 2015
    Co-Authors: Annie M. Whitaker, Nicholas W. Gilpin
    Abstract:

    Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as 'Avoiders' or 'Non-Avoiders' post-stress based on avoidance of Predator-Odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this Predator Odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a Predator-paired context relative to those that do not. Rats were exposed to Predator Odor stress paired with a context and tested for avoidance (24h and 11days), anxiety-like behavior (48h and 5days) and HPA activation following stress. Control animals were exposed to room air. Predator Odor stress produced avoidance in approximately 65% of the animals at 24h that persisted 11days post-stress. Both Avoiders and Non-Avoiders exhibited a heightened anxiety-like behavior at 48h and 5days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following Predator Odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and build on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders.

Joyce Besheer - One of the best experts on this subject based on the ideXlab platform.

  • increased alcohol self administration following exposure to the Predator Odor tmt in active coping female rats
    Behavioural Brain Research, 2021
    Co-Authors: Laura C Ornelas, Ryan E Tyler, Preethi Irukulapati, Sudheesha Paladugu, Joyce Besheer
    Abstract:

    Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid. Additionally, individual differences in response to stress suggest resilient and susceptible populations. The current study exposed male and female Long Evans rats to the synthetically produced Predator Odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to examine individual differences in stress-reactive behaviors (digging and immobility) and whether these differences were related to subsequent alcohol drinking. Male and female Long Evans rats were trained on operant alcohol self-administration. After 9 sessions, rats underwent exposure to TMT or water (Control) in a distinct context. 6 days after TMT exposure, rats underwent re-exposure to the TMT-paired context (without TMT), and a series of behavioral assessments (acoustic startle, zero maze, light/dark box), after which rats resumed alcohol self-administration. TMT subgroups were created using a ratio of digging to immobility behavior during TMT exposure and rats with a ratio score 1.0 were grouped into TMT-1 (low digging/high immobility) or TMT-2 (high digging/low immobility), respectively. All male rats exposed to TMT met criteria for TMT-1, while female rats were divided into the two subgroups. In females, high digging/low immobility behavior during TMT exposure (TMT-2) was related to increased alcohol self-administration, but this was not observed in males or females that engaged in low digging/high immobility (TMT-1). These data show that individual differences in stress-reactivity can lead to lasting behavioral changes which may lead to a better understanding of increases in alcohol drinking following stress in females.

  • The synthetically produced Predator Odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and alters basolateral amygdala response to alcohol in rats
    Psychopharmacology, 2020
    Co-Authors: Viren H. Makhijani, Franklin, Kalynn Voorhies, Brayden Fortino, Joyce Besheer
    Abstract:

    Post-traumatic stress disorder (PTSD) is a psychiatric illness that can increase the risk for developing an alcohol use disorder (AUD). While clinical data has been useful in identifying similarities in the neurobiological bases of these disorders, preclinical models are essential for understanding the mechanism(s) by which stressors increase the risk for escalated alcohol consumption. The purpose of these studies was to examine if exposure of male Long-Evans rats to the synthetically derived Predator Odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT; a component of fox feces) would increase sweetened alcohol self-administration, potentially by facilitating transfer of salience towards cues, and alter neuronal response to alcohol as measured by the immediate early gene c-Fos. In experiment 1, rats exposed to repeated (4×) TMT showed reductions in port entries in Pavlovian conditioned approach and increases in sweetened alcohol self-administration. In experiment 2, rats exposed to repeated TMT showed blunted basolateral amygdala c-Fos response to alcohol. In experiment 3, rats exposed to single, but not repeated TMT, showed increases in sweetened alcohol self-administration, and no change in anxiety-like behavior or hyperarousal. In experiment 4, rats continued to show a significant corticosterone response to TMT after repeated exposures. In summary, exposure of male rats to TMT can cause escalations in sweetened alcohol self-administration and reduction in BLA response to alcohol. These studies outline and utilize a novel preclinical model that can be used to further neurobiological understanding of the emergence of escalated alcohol consumption following stress exposure.

  • increased alcohol self administration following exposure to the Predator Odor tmt in high stress reactive female rats
    bioRxiv, 2020
    Co-Authors: Laura C Ornelas, Ryan E Tyler, Preethi Irukulapati, Sudheesha Paladugu, Joyce Besheer
    Abstract:

    Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid. Additionally, individual differences in response to stress suggest resilient and susceptible populations. The current study exposed male and female Long Evans rats to the synthetically produced Predator Odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to examine individual differences in stress-reactive behaviors (digging and immobility) and whether these differences could predict lasting consequences of TMT and increases in alcohol drinking. Male and female Long Evans rats were trained on operant alcohol self-administration. After 9 sessions, rats underwent exposure to TMT or water (Control) in a distinct context. 6 days after TMT exposure, rats underwent re-exposure to the TMT-paired context (without TMT), and a series of behavioral assessments (acoustic startle, zero maze, light/dark box), after which rats resumed alcohol self-administration. Rats were divided into two TMT-subgroups using a ratio of digging and immobility behavior during TMT exposure: TMT-subgroup 1 (low digging/immobility ratio) and TMT-subgroup 2 (high digging/immobility ratio). Digging/immobility ratio scores predicted elevated corticosterone levels during TMT exposure and reactivity during context re-exposure in males and females (TMT-subgroup 2), as well as elevated corticosterone levels after context re-exposure and hyperarousal behavior in females (TMT-subgroup 1). Furthermore, TMT stress reactivity predicted increases in alcohol self-administration, specifically in females. These data show that stress-reactivity can predict lasting behavioral changes which may lead to a better understanding of increases in alcohol drinking following stress in females and that individual differences in stress-reactive behaviors using TMT may be helpful to understand resilience/susceptibility to the lasting consequences of stress.

  • exposure to the Predator Odor tmt induces early and late differential gene expression related to stress and excitatory synaptic function throughout the brain in male rats
    Genes Brain and Behavior, 2020
    Co-Authors: Ryan E Tyler, Laura C Ornelas, Benjamin Z S Weinberg, Dennis F Lovelock, Joyce Besheer
    Abstract:

    Persistent changes in brain stress and glutamatergic function are associated with post-traumatic stress disorder (PTSD). Rodent exposure to the Predator Odor trimethylthiazoline (TMT) is an innate stressor that produces lasting behavioral consequences relevant to PTSD. As such, the goal of the present study was to assess early (6 hours and 2 days-Experiment 1) and late (4 weeks-Experiment 2) changes to gene expression (RT-PCR) related to stress and excitatory function following TMT exposure in male, Long-Evans rats. During TMT exposure, rats engaged in stress reactive behaviors, including digging and immobility. Further, the TMT group displayed enhanced exploration and mobility in the TMT-paired context 1 week after exposure, suggesting a lasting contextual reactivity. Gene expression analyses revealed upregulated FKBP5 6 hours post-TMT in the hypothalamus and dorsal hippocampus. Two days after TMT, GRM3 was downregulated in the prelimbic cortex and dorsal hippocampus, but upregulated in the nucleus accumbens. This may reflect an early stress response (FKBP5) that resulted in later glutamatergic adaptation (GRM3). Finally, another experiment 4 weeks after TMT exposure showed several differentially expressed genes known to mediate excitatory tripartite synaptic function in the prelimbic cortex (GRM5, DLG4 and SLC1A3 upregulated), infralimbic cortex (GRM2 downregulated, Homer1 upregulated), nucleus accumbens (GRM7 and SLC1A3 downregulated), dorsal hippocampus (FKBP5 and NR3C2 upregulated, SHANK3 downregulated) and ventral hippocampus (CNR1, GRM7, GRM5, SHANK3 and Homer1 downregulated). These data show that TMT exposure induces stress and excitatory molecular adaptations, which could help us understand the persistent glutamatergic dysfunction observed in PTSD.

  • the synthetically produced Predator Odor 2 5 dihydro 2 4 5 trimethylthiazoline increases alcohol self administration and alters basolateral amygdala response to alcohol in rats
    bioRxiv, 2020
    Co-Authors: Viren H. Makhijani, Brayden Fortino, Janay P Franklin, Kalynn Van Voorhies, Joyce Besheer
    Abstract:

    Post-traumatic stress disorder (PTSD) is a psychiatric illness that can increase the risk for developing an alcohol use disorder (AUD). While clinical data has been useful in identifying similarities in the neurobiological bases of these disorders, preclinical models are essential for understanding the mechanism(s) by which PTSD increases the risk of developing AUD. The purpose of these studies was to examine if exposure of male Long-Evans rats to the synthetically produced Predator Odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) would increase alcohol self-administration, potentially by facilitating transfer of salience towards cues, and alter neuronal response to alcohol as measured by the immediate early gene c-Fos. In Experiment 1 rats exposed to repeated (4x) TMT showed reductions in goal-tracking behavior in Pavlovian conditioned approach, and increases in alcohol self-administration. In Experiment 2 rats exposed to repeated TMT showed blunted basolateral amygdala c-Fos response to alcohol, and increased correlation between medial prefrontal cortex and amygdala subregions. In Experiment 3 rats exposed to single, but not repeated TMT showed increases in alcohol self-administration, and no change in anxiety-like behavior or hyperarousal. In Experiment 4, rats showed no habituation of corticosterone response after 4 TMT exposures. In summary, exposure of male rats to TMT can cause escalations in alcohol self-administration, reductions in goal-tracking behavior, and reduction in BLA response to alcohol. These studies outline and utilize a novel preclinical model that can be used to further neurobiological understanding of the relationship between PTSD and AUD.

Lorey K. Takahashi - One of the best experts on this subject based on the ideXlab platform.

  • Olfactory systems and neural circuits that modulate Predator Odor fear.
    Frontiers in behavioral neuroscience, 2014
    Co-Authors: Lorey K. Takahashi
    Abstract:

    When prey animals detect the Odor of a Predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process Predator Odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie Predator Odor fear. For instance, the main (MOS) and accessory olfactory systems (AOS) detect Predator Odors and different types of Predator Odors are sensed by specific receptors located in either the MOS or AOS. However, complex Predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray (DPAG), paraventricular nucleus (PVN) of the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in Predator Odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA) stress hormone secretion. The MeA also plays a key role in Predator Odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior Predator Odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus (VHC) appear prominently involved in Predator Odor fear behavior. The basolateral amygdala (BLA), medial hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some but not all Predator Odors. Future research that characterizes how distinct Predator Odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse Predator Odors activate fear.

  • Predator Odor fear conditioning: current perspectives and new directions.
    Neuroscience and biobehavioral reviews, 2008
    Co-Authors: Lorey K. Takahashi, Megan M. Chan, Mark L. Pilar
    Abstract:

    Predator Odor fear conditioning involves the use of a natural unconditioned stimulus, as opposed to aversive electric foot-shock, to obtain novel information on the neural circuitry associated with emotional learning and memory. Researchers are beginning to identify brain sites associated with conditioned contextual fear such as the ventral anterior olfactory nucleus, dorsal premammillary nucleus, ventrolateral periaqueductal gray, cuneiform nucleus, and locus coeruleus. In addition, a few studies have reported an involvement of the basolateral and medial nucleus of the amygdala and hippocampus in fear conditioning. However, several important issues concerning the effectiveness of different Predator Odor unconditioned stimuli to produce fear conditioning, the precise role of brain nuclei in fear conditioning, and the general relation between the current Predator Odor and the traditional electric foot-shock fear conditioning procedures remain to be satisfactorily addressed. This review discusses the major behavioral results in the current Predator Odor fear conditioning literature and introduces two novel contextual and auditory fear conditioning models using cat Odor. The new models provide critical information on the acquisition of conditioned fear behavior during training and the expression of conditioned responses in the retention test. Future studies adopting fear conditioning procedures that incorporate measures of both unconditioned and conditioned responses during training may lead to broad insights into Predator Odor fear conditioning and identify specific brain nuclei mediating conditioned stimulus-Predator Odor unconditioned stimulus associations.

  • Predator Odor-induced conditioned fear involves the basolateral and medial amygdala.
    Behavioral neuroscience, 2007
    Co-Authors: Lorey K. Takahashi, David T. Hubbard, Iris Lee, Yasmin Dar, Sara M. Sipes
    Abstract:

    The basolateral (BLA) and medial nucleus (MeA) of the amygdala participate in the modulation of unconditioned fear induced by Predator Odor. However, the specific role of these amygdalar nuclei in Predator Odor-induced fear memory is not known. Therefore, fiber-sparing lesions or temporary inactivation of the BLA or MeA were made either prior to or after exposure to cat Odor, and conditioned contextual fear behavior was examined the next day. BLA and MeA lesions produced significant reductions in cat Odor-induced unconditioned and conditioned fear-related behavior. In addition, temporary pharmacological neural inactivation methods occurring after exposure to cat Odor revealed subtle behavioral alterations indicative of a role of the BLA in fear memory consolidation but not memory retrieval. In contrast, the MeA appears to play a specific role in retrieval but not consolidation. Results show that the BLA participates in the conditioned and unconditioned cat Odor stimulus association that underlies fear memory, underscore a novel role of the MeA in Predator Odor contextual conditioning, and demonstrate different roles of the BLA and MeA in modulating consolidation and retrieval of Predator Odor fear memory.

  • The smell of danger: A behavioral and neural analysis of Predator Odor-induced fear
    Neuroscience and biobehavioral reviews, 2005
    Co-Authors: Lorey K. Takahashi, Brandy R. Nakashima, Hyechong Hong, Kendra Watanabe
    Abstract:

    The Odors of Predators used in animal models provide, in addition to electric footshock, an important means to investigate the neurobiology of fear. Studies indicate that cat Odor and trimethylthiazoline (TMT), a synthetic compound isolated from fox feces, are often presented to rodents to induce fear-related responses including freezing, avoidance, stress hormone and, in some tests, risk assessment behavior. Furthermore, we report that different amounts of cat Odor impregnated on small-, medium-, or large-sized cloths impact the display of fear-related behavior when presented to rats. That is, rats exposed to a large cat Odor containing cloth exhibit an increase in fear behavior, particularly freezing, which remains at high levels in habituation tests administered over a period of 7 days. The large cloth also induces a long-lasting increase in avoidance behavior during repeated habituation and extinction tests. A review of the brain regions involved in Predator Odor-induced fear behavior indicates a modulatory role of the medial amygdala, bed nucleus of the stria terminalis, and dorsal premammillary nucleus. In addition, the basolateral amygdala is involved in fear behavior induced by cat Odor but not TMT, and the central amygdala does not appear to play a major behavioral role in Predator Odor-induced fear. Future research involving the use of Predator Odor is likely to rapidly expand knowledge on the neurobiology of fear, which has implications for understanding fear-related psychopathology.

  • Medial amygdala modulation of Predator Odor-induced unconditioned fear in the rat.
    Behavioral neuroscience, 2004
    Co-Authors: Thomas L Maglinao, Lorey K. Takahashi
    Abstract:

    This study examined the participation of the medial amygdala (MeA) in unconditioned fear. Rats received ibotenic acid lesions in the MeA or central amygdala (CeA) prior to cat-Odor exposure. MeA-lesioned rats exhibited a significant reduction in freezing duration and made frequent contact with a cloth containing cat Odor. In contrast, CeA lesions had no significant effects on unconditioned fear. The freezing reduction produced by MeA lesions was not due to a performance deficit because MeA-lesioned rats, unlike CeA-lesioned rats, were capable of freezing in postshock test intervals. Furthermore, MeA lesions did not alter olfactory function and general locomotor activity. Results demonstrate that the MeA plays a major role in modulating Predator Odor-induced unconditioned fear.

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  • Postnatal exposure to synthetic Predator Odor (TMT) induces quantitative modification in fear-related behaviors during adulthood without change in corticosterone levels.
    Behavioural brain research, 2010
    Co-Authors: Romain Hacquemand, Laurence Jacquot, Gregory Pourié, Gérard Brand
    Abstract:

    Environmental stimuli and adverse experiences in early life may result in behavioral and physiological changes in adulthood. In several animal species, the Odors cues are crucial in the setting of adaptive behaviors, especially towards Predators. However, little is known about the effects of postnatal exposure to Predator Odor on the later physiological and behavioral responses to this natural stressor. Thus, the aim of this study was to investigate the effects of a postnatal exposure to synthetic Predator Odor (TMT) in mice pups on later adult fear-related behaviors and corticosterone levels in response to this specific stimulus. Pups postnatally exposed to only water showed later in adult life behavioral responses when exposed to TMT that were statistically different from mice that were exposed as neonates to TMT. In addition, mice exposed as neonates to TMT showed a decrease of fear-related behaviors while no differences occurred in the corticosterone levels between both groups.

  • Enhancement of spatial learning by Predator Odor in mice: involvement of amygdala and hippocampus.
    Neurobiology of Learning and Memory, 2010
    Co-Authors: Emmanuel Galliot, Maryline Levaillant, Elidie Beard, Jean-louis Millot, Gregory Pourié
    Abstract:

    Olfaction has particular links with learning and memory compared with other sensory cues, due to the interrelations between their neural circuitry. The present study deals with the effects of a putative stressor (i.e. a Predator Odor) on visuo-spatial learning in mice. Firstly, the results show that a Predator Odor spread during the Morris water maze task led to learning enhancement. In addition, a stereotaxic approach was used to investigate the involvement of the amygdala in this hippocampus-dependent type of learning. Thus, the performance of mice in visuo-spatial learning under Predator Odor conditions was dramatically reduced by an ibotenate bilateral amygdala lesion. The involvement of the amygdala was confirmed by a reduced expression of c-fos in the CA1 hippocampus of amygdala-lesioned mice at the end of the learning procedure. Mild exposure to a Predator Odor during hippocampus-dependent learning therefore leads to an enhancement of performance through the co-activation of the amygdala, probably by a stress mediated mechanism.