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Jaak Panksepp - One of the best experts on this subject based on the ideXlab platform.
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The Psycho-Neurology of Cross-Species Affective/Social Neuroscience: Understanding Animal Affective States as a Guide to Development of Novel Psychiatric Treatments.
Current topics in behavioral neurosciences, 2016Co-Authors: Jaak PankseppAbstract:During the past half century of research with preclinical animal models, affective neuroscience has helped identify and illuminate the functional neuroanatomies and neurochemistries of seven primary process, i.e., genetically provided emotional systems of mammalian brains. All are subcortically localized, allowing animal models to guide the needed behavioral and neuroscientific analyses at levels of detail that cannot be achieved through human research, including modern brain imaging. They consist of the following neuronal processes: SEEKING/Enthusiasm, RAGE/Anger, FEAR/Anxiety, sexual LUST/Passion, maternal CARE/Nurturance, Separation-Distress PANIC/Grief and PLAY/Social Joy. Several of these systems figure heavily in social bonding. I will focus here especially on the genesis of depression. Its genesis is significantly influenced by (i) sustained overactivity of the Separation-Distress PANIC system reflecting severed social bonds and the excessive “psychological pain” of loneliness that can, if sustained, lead to a downward cascade known as psychological despair, and (ii) the despair phase that follows the acute PANIC response, which is characterized by abnormally low activity of the SEEKING, the so-called brain reward networks, leading to amotivational states that characterize depression. Depressive affect is promoted by such brain affective mechanisms of social attachments and social loss as well as diminished arousability of the SEEKING system, leading to chronic dysphoria. To understand why depression feels so bad, we must understand the neural mechanisms that mediate such social feelings.
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Preclinical modeling of primal emotional affects (Seeking, Panic and Play): gateways to the development of new treatments for depression.
Psychopathology, 2014Co-Authors: Jaak Panksepp, Yoram YovellAbstract:Mammalian brains contain at least 7 primal emotional systems - SEEKING, RAGE, FEAR, LUST, CARE, PANIC and PLAY (capitalization reflects a proposed primary-process terminology, to minimize semantic confusions and mereological fallacies). These systems help organisms feel affectively balanced (e.g. euthymic) and unbalanced (e.g. depressive, irritable, manic), providing novel insights for understanding human psychopathologies. Three systems are especially important for understanding depression: The Separation Distress (PANIC) system mediates the psychic pain of Separation Distress (i.e. excessive sadness and grief), which can be counteracted by minimizing PANIC arousals (as with low-dose opioids). Depressive dysphoria also arises from reduced brain reward-seeking and related play urges (namely diminished enthusiasm (SEEKING) and joyful exuberance (PLAY) which promote sustained amotivational states). We describe how an understanding of these fundamental emotional circuits can promote the development of novel antidepressive therapeutics - (i) low-dose buprenorphine to counteract depression and suicidal ideation emanating from too much psychic pain (PANIC overarousal), (ii) direct stimulation of the SEEKING system to counteract amotivational dysphoria, and (iii) the discovery and initial clinical testing of social-joy-promoting molecules derived from the analysis of the PLAY system.
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differential ultrasonic indices of Separation Distress in the presence and absence of maternal cues in infant rats bred for high and low positive social affect
Acta Neuropsychiatrica, 2013Co-Authors: Paolo Iacobucci, Valentina Colonnello, Thomas Fuchs, Laura Dantuono, Jaak PankseppAbstract:OBJECTIVE: Preclinical models of human mood disorders commonly focus on the study of negative affectivity, without comparably stressing the role of positive affects and their ability to promote resilient coping styles. We evaluated the role of background constitutional affect of rats by studying the Separation and reunion responses of infants from low and high positive affect genetic lines (i.e., differentially selected for High and Low 50 kHz ultrasonic vocalisations (USVs). METHODS: Infants from Low and High 50 kHz USV breeding lines were isolated from mothers and exposed to either social (familiar or unfamiliar bedding) or neutral (clean bedding) odour cues between two short isolation periods, and tested in homeothermic and hypothermic ambient temperatures. Negative affect was estimated by monitoring Separation Distress calls (35-45 kHz USVs). RESULTS: Low Line pups called at higher rates than High Line, and their rates were stable regardless of odour cue. In contrast, High Line pups increased vocalisations during the second compared with the first isolation periods and during exposure to both familiar and unfamiliar odour cues, but not to neutral odour. Furthermore, the greatest increase in USV emission was seen in the second isolation period following exposure to the unfamiliar odour. However, both lines showed comparable elevated Distress USVs to the thermal stressor. CONCLUSION: High Line animals, selected for a positive affective phenotype (50 kHz USVs), exhibited reduced Separation anxiety responses in infancy, making this a promising animal model for the role of constitutional affective states in emotional responsivity and potential resilience against emotional disorders.
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Social Support and Pain: How Does the Brain Feel the Ache of a Broken Heart?
Journal of Cancer Pain & Symptom Palliation, 2011Co-Authors: Jaak PankseppAbstract:Studies of the animal brain have long suggested that the pain of social loss evolved from the capacity to feel physi- cal pain. The most robust communality is the fact that both Separation Distress and physical pain share some brain systems, especially the opioid modulation of the affective intensity of both. The following essay summarizes this ev- idence and discusses some implications for pain management. (Article copies available for a fee from The Haworth Document Delivery Service: 1-800-HAWORTH. E-mail address: Website: © 2005 by The Haworth Press, Inc. All rights reserved.)
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analysis of the disruption of maternal social bonds in octodon degus Separation Distress in restricted reunion tests
Developmental Psychobiology, 2011Co-Authors: Valentina Colonnello, Paolo Iacobucci, Jaak PankseppAbstract:Octodon degus is a social caviomorph species that exhibits strong social bonds and robust Distress responses to maternal Separation. To understand the impact of early social isolation on social motivation, we investigated how social isolation during infancy, associated with repeated restricted interactions with mother and siblings, altered social motivation in young degus. In Experiment 1, three treatments were compared: complete isolation (ISOLATED group), nearly complete isolation, with daily half hour partition-restricted reunions with the mother and siblings (RESTRICTED group), and social-housing with the mother and siblings (FAMILY group). After 10 days of treatment, all subjects underwent a 5-day choice test between mothers and unfamiliar females. During the treatment period, the RESTRICTED animals emitted more isolation calls and spent more time close to the partition that separated them from mothers than ISOLATED animals. During the first social-choice day, FAMILY reared animals showed a preference for the mother for a few minutes, while the RESTRICTED animals preferred the mother for the whole session. Totally ISOLATED pups exhibited no social preferences. Since during successive testing periods the isolation calls decreased over the days, in Experiment 2 we investigated whether this decline was related to age or habituation to testing procedures. Animals were observed during a single exposure to isolation (ISOLATED) or restricted-reunion (RESTRICTED) at PND 21 and 31. The decrease of vocalizations was due to an age-effect. The findings clarify the nature of social bonds in degus. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 53:657–669, 2011.
Klaus A. Miczek - One of the best experts on this subject based on the ideXlab platform.
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Glutamatergic and GABAergic modulations of ultrasonic vocalizations during maternal Separation Distress in mouse pups
Psychopharmacology, 2009Co-Authors: Aki Takahashi, Dawnya Zitzman Bohager, Sara Faccidomo, Terry Clayton, James M. Cook, Klaus A. MiczekAbstract:Introduction Dysregulation of GABAergic inhibition and glutamatergic excitation has been implicated in exaggerated anxiety. Mouse pups emit Distress-like ultrasonic vocalizations (USVs) when they are separated from their dam/siblings, and this behavior is reduced by benzodiazepines (BZs) which modulate GABAergic inhibition. The roles of glutamate receptors on USVs remain to be investigated. Materials and methods We examined the roles of glutamate receptor subtypes on mouse pup USVs using N -methyl- d -aspartate (NMDA) receptor antagonists with different affinities [dizocilpine (MK-801), memantine, and neramexane] and group II metabotropic glutamate receptor agonist (LY-379268) and antagonist (LY-341495). These effects were compared with classic BZs: flunitrazepam, bromazepam, and chlordiazepoxide. To assess the role of GABA_A receptor subunits on USVs, drugs that have preferential actions at different GABA_A-α subunits (L-838417 and QH-ii-066) were tested. Seven-day-old CFW mouse pups were separated from their dam and littermates and placed individually on a 19°C test platform for 4 min. Grid crossings and body rolls were measured in addition to USVs. Results Dizocilpine dose-dependently reduced USVs, whereas memantine and neramexane showed biphasic effects and enhanced USVs at low to moderate doses. The NMDA receptor antagonists increased locomotion. LY-379268 reduced USVs but also suppressed locomotion. All BZs reduced USVs and increased motor incoordination. Neither L-838417 nor QH-ii-066 changed USVs, but both induced motor incoordination. Conclusion Low-affinity NMDA receptor antagonists, but not the high-affinity antagonist, enhanced mouse pup Distress calls, which may be reflective of an anxiety-like state. BZs reduced USVs but also induced motor incoordination, possibly mediated by the α5 subunit containing GABA_A receptors.
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glutamatergic and gabaergic modulations of ultrasonic vocalizations during maternal Separation Distress in mouse pups
Psychopharmacology, 2009Co-Authors: Aki Takahashi, Dawnya Zitzman Bohager, Sara Faccidomo, James M. Cook, Terrill Scott Clayton, Klaus A. MiczekAbstract:Introduction Dysregulation of GABAergic inhibition and glutamatergic excitation has been implicated in exaggerated anxiety. Mouse pups emit Distress-like ultrasonic vocalizations (USVs) when they are separated from their dam/siblings, and this behavior is reduced by benzodiazepines (BZs) which modulate GABAergic inhibition. The roles of glutamate receptors on USVs remain to be investigated.
Sara Faccidomo - One of the best experts on this subject based on the ideXlab platform.
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Glutamatergic and GABAergic modulations of ultrasonic vocalizations during maternal Separation Distress in mouse pups
Psychopharmacology, 2009Co-Authors: Aki Takahashi, Dawnya Zitzman Bohager, Sara Faccidomo, Terry Clayton, James M. Cook, Klaus A. MiczekAbstract:Introduction Dysregulation of GABAergic inhibition and glutamatergic excitation has been implicated in exaggerated anxiety. Mouse pups emit Distress-like ultrasonic vocalizations (USVs) when they are separated from their dam/siblings, and this behavior is reduced by benzodiazepines (BZs) which modulate GABAergic inhibition. The roles of glutamate receptors on USVs remain to be investigated. Materials and methods We examined the roles of glutamate receptor subtypes on mouse pup USVs using N -methyl- d -aspartate (NMDA) receptor antagonists with different affinities [dizocilpine (MK-801), memantine, and neramexane] and group II metabotropic glutamate receptor agonist (LY-379268) and antagonist (LY-341495). These effects were compared with classic BZs: flunitrazepam, bromazepam, and chlordiazepoxide. To assess the role of GABA_A receptor subunits on USVs, drugs that have preferential actions at different GABA_A-α subunits (L-838417 and QH-ii-066) were tested. Seven-day-old CFW mouse pups were separated from their dam and littermates and placed individually on a 19°C test platform for 4 min. Grid crossings and body rolls were measured in addition to USVs. Results Dizocilpine dose-dependently reduced USVs, whereas memantine and neramexane showed biphasic effects and enhanced USVs at low to moderate doses. The NMDA receptor antagonists increased locomotion. LY-379268 reduced USVs but also suppressed locomotion. All BZs reduced USVs and increased motor incoordination. Neither L-838417 nor QH-ii-066 changed USVs, but both induced motor incoordination. Conclusion Low-affinity NMDA receptor antagonists, but not the high-affinity antagonist, enhanced mouse pup Distress calls, which may be reflective of an anxiety-like state. BZs reduced USVs but also induced motor incoordination, possibly mediated by the α5 subunit containing GABA_A receptors.
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glutamatergic and gabaergic modulations of ultrasonic vocalizations during maternal Separation Distress in mouse pups
Psychopharmacology, 2009Co-Authors: Aki Takahashi, Dawnya Zitzman Bohager, Sara Faccidomo, James M. Cook, Terrill Scott Clayton, Klaus A. MiczekAbstract:Introduction Dysregulation of GABAergic inhibition and glutamatergic excitation has been implicated in exaggerated anxiety. Mouse pups emit Distress-like ultrasonic vocalizations (USVs) when they are separated from their dam/siblings, and this behavior is reduced by benzodiazepines (BZs) which modulate GABAergic inhibition. The roles of glutamate receptors on USVs remain to be investigated.
Dawnya Zitzman Bohager - One of the best experts on this subject based on the ideXlab platform.
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Glutamatergic and GABAergic modulations of ultrasonic vocalizations during maternal Separation Distress in mouse pups
Psychopharmacology, 2009Co-Authors: Aki Takahashi, Dawnya Zitzman Bohager, Sara Faccidomo, Terry Clayton, James M. Cook, Klaus A. MiczekAbstract:Introduction Dysregulation of GABAergic inhibition and glutamatergic excitation has been implicated in exaggerated anxiety. Mouse pups emit Distress-like ultrasonic vocalizations (USVs) when they are separated from their dam/siblings, and this behavior is reduced by benzodiazepines (BZs) which modulate GABAergic inhibition. The roles of glutamate receptors on USVs remain to be investigated. Materials and methods We examined the roles of glutamate receptor subtypes on mouse pup USVs using N -methyl- d -aspartate (NMDA) receptor antagonists with different affinities [dizocilpine (MK-801), memantine, and neramexane] and group II metabotropic glutamate receptor agonist (LY-379268) and antagonist (LY-341495). These effects were compared with classic BZs: flunitrazepam, bromazepam, and chlordiazepoxide. To assess the role of GABA_A receptor subunits on USVs, drugs that have preferential actions at different GABA_A-α subunits (L-838417 and QH-ii-066) were tested. Seven-day-old CFW mouse pups were separated from their dam and littermates and placed individually on a 19°C test platform for 4 min. Grid crossings and body rolls were measured in addition to USVs. Results Dizocilpine dose-dependently reduced USVs, whereas memantine and neramexane showed biphasic effects and enhanced USVs at low to moderate doses. The NMDA receptor antagonists increased locomotion. LY-379268 reduced USVs but also suppressed locomotion. All BZs reduced USVs and increased motor incoordination. Neither L-838417 nor QH-ii-066 changed USVs, but both induced motor incoordination. Conclusion Low-affinity NMDA receptor antagonists, but not the high-affinity antagonist, enhanced mouse pup Distress calls, which may be reflective of an anxiety-like state. BZs reduced USVs but also induced motor incoordination, possibly mediated by the α5 subunit containing GABA_A receptors.
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glutamatergic and gabaergic modulations of ultrasonic vocalizations during maternal Separation Distress in mouse pups
Psychopharmacology, 2009Co-Authors: Aki Takahashi, Dawnya Zitzman Bohager, Sara Faccidomo, James M. Cook, Terrill Scott Clayton, Klaus A. MiczekAbstract:Introduction Dysregulation of GABAergic inhibition and glutamatergic excitation has been implicated in exaggerated anxiety. Mouse pups emit Distress-like ultrasonic vocalizations (USVs) when they are separated from their dam/siblings, and this behavior is reduced by benzodiazepines (BZs) which modulate GABAergic inhibition. The roles of glutamate receptors on USVs remain to be investigated.
Aki Takahashi - One of the best experts on this subject based on the ideXlab platform.
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Glutamatergic and GABAergic modulations of ultrasonic vocalizations during maternal Separation Distress in mouse pups
Psychopharmacology, 2009Co-Authors: Aki Takahashi, Dawnya Zitzman Bohager, Sara Faccidomo, Terry Clayton, James M. Cook, Klaus A. MiczekAbstract:Introduction Dysregulation of GABAergic inhibition and glutamatergic excitation has been implicated in exaggerated anxiety. Mouse pups emit Distress-like ultrasonic vocalizations (USVs) when they are separated from their dam/siblings, and this behavior is reduced by benzodiazepines (BZs) which modulate GABAergic inhibition. The roles of glutamate receptors on USVs remain to be investigated. Materials and methods We examined the roles of glutamate receptor subtypes on mouse pup USVs using N -methyl- d -aspartate (NMDA) receptor antagonists with different affinities [dizocilpine (MK-801), memantine, and neramexane] and group II metabotropic glutamate receptor agonist (LY-379268) and antagonist (LY-341495). These effects were compared with classic BZs: flunitrazepam, bromazepam, and chlordiazepoxide. To assess the role of GABA_A receptor subunits on USVs, drugs that have preferential actions at different GABA_A-α subunits (L-838417 and QH-ii-066) were tested. Seven-day-old CFW mouse pups were separated from their dam and littermates and placed individually on a 19°C test platform for 4 min. Grid crossings and body rolls were measured in addition to USVs. Results Dizocilpine dose-dependently reduced USVs, whereas memantine and neramexane showed biphasic effects and enhanced USVs at low to moderate doses. The NMDA receptor antagonists increased locomotion. LY-379268 reduced USVs but also suppressed locomotion. All BZs reduced USVs and increased motor incoordination. Neither L-838417 nor QH-ii-066 changed USVs, but both induced motor incoordination. Conclusion Low-affinity NMDA receptor antagonists, but not the high-affinity antagonist, enhanced mouse pup Distress calls, which may be reflective of an anxiety-like state. BZs reduced USVs but also induced motor incoordination, possibly mediated by the α5 subunit containing GABA_A receptors.
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glutamatergic and gabaergic modulations of ultrasonic vocalizations during maternal Separation Distress in mouse pups
Psychopharmacology, 2009Co-Authors: Aki Takahashi, Dawnya Zitzman Bohager, Sara Faccidomo, James M. Cook, Terrill Scott Clayton, Klaus A. MiczekAbstract:Introduction Dysregulation of GABAergic inhibition and glutamatergic excitation has been implicated in exaggerated anxiety. Mouse pups emit Distress-like ultrasonic vocalizations (USVs) when they are separated from their dam/siblings, and this behavior is reduced by benzodiazepines (BZs) which modulate GABAergic inhibition. The roles of glutamate receptors on USVs remain to be investigated.
