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Charlotte A Cornil - One of the best experts on this subject based on the ideXlab platform.

  • estradiol rapidly activates male sexual behavior and affects brain monoamine levels in the quail brain
    Behavioural Brain Research, 2006
    Co-Authors: Christina Dalla, Z Papadopouloudaifoti, Michelle Baillien, Charlotte A Cornil, Jacques Balthazart
    Abstract:

    Abstract Steroids are generally viewed as transcription factors binding to intracellular receptors and activating gene transcription. Rapid cellular Effects mediated via non-genomic mechanisms have however been identified and one report showed that injections of estradiol rapidly stimulate chemoinvestigation and mounting behavior in castrated male rats. It is not known whether such Effects take place in other species and what are the cellular underlying mechanisms. We show here that a single injection of estradiol (500 μg/kg) rapidly and transiently activates copulatory behavior in castrated male quail pre-treated with a dose of testosterone Behaviorally inEffective by itself. The maximal Behavioral Effect was observed after 15 min. In a second experiment, the brain of all subjects was immediately collected after Behavioral tests performed 15 min after injection. The preoptic area—hypothalamus (HPOA), hindbrain, telencephalon and cerebellum were isolated and monoamines measured by HPLC-ED. Estradiol increased levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/serotonin ratios in the telencephalon and hindbrain independently of whether animals had mated or not. Estradiol also affected these measures in HPOA and cerebellum but this Effect was correlated with the level of sexual activity so that significant Effects of the treatment only appeared when sexual activity was used as a covariate. Interactions between estradiol Effects and sexual activity were also observed for dopamine in the HPOA and for serotonin in the hindbrain and cerebellum. Together, these data demonstrate that a single estradiol injection rapidly activates male sexual behavior in quail and that this Behavioral Effect is correlated with changes in monoaminergic activity.

Mark G. Baxter - One of the best experts on this subject based on the ideXlab platform.

  • Behavioral Effect of Chemogenetic Inhibition Is Directly Related to Receptor Transduction Levels in Rhesus Monkeys
    The Journal of Neuroscience, 2018
    Co-Authors: Nicholas A. Upright, Stephen W. Brookshire, Wendy Schnebelen, Christienne G. Damatac, Patrick R. Hof, Philip G. F. Browning, Paula L. Croxson, Peter H. Rudebeck, Mark G. Baxter
    Abstract:

    We used inhibitory DREADDs (designer receptors exclusively activated by designer drugs) to reversibly disrupt dorsolateral prefrontal cortex (dlPFC) function in male rhesus monkeys. Monkeys were tested on a spatial delayed response task to assess working memory function after intramuscular injection of either clozapine-N-oxide (CNO) or vehicle. CNO injections given before DREADD transduction were without Effect on behavior. rAAV5/hSyn-hM4Di-mCherry was injected bilaterally into the dlPFC of five male rhesus monkeys, to produce neuronal expression of the inhibitory (Gi-coupled) DREADD receptor. We quantified the percentage of DREADD-transduced cells using stereological analysis of mCherry-immunolabeled neurons. We found a greater number of immunolabeled neurons in monkeys that displayed CNO-induced Behavioral impairment after DREADD transduction compared with monkeys that showed no Behavioral Effect after CNO. Even in monkeys that showed reliable Effects of CNO on behavior after DREADD transduction, the number of prefrontal neurons transduced with DREADD receptor was on the order of 3% of total prefrontal neurons counted. This level of histological analysis facilitates our understanding of Behavioral Effects, or lack thereof, after DREADD vector injection in monkeys. It also implies that a functional silencing of a relatively small fraction of dlPFC neurons, albeit in a widely distributed area, is sufficient to disrupt spatial working memory.SIGNIFICANCE STATEMENT Cognitive domains such as working memory and executive function are mediated by the dorsolateral prefrontal cortex (dlPFC). Impairments in these domains are common in neurodegenerative diseases as well as normal aging. The present study sought to measure deficits in a spatial delayed response task following activation of viral-vector transduced inhibitory DREADD (designer receptor exclusively activated by designer drug) receptors in rhesus macaques and compare this to the level of transduction in dlPFC using stereology. We found a significant relationship between the extent of DREADD transduction and the magnitude of Behavioral deficit following administration of the DREADD actuator compound clozapine-N-oxide (CNO). These results demonstrate it will be critical to validate transduction to ensure DREADDs remain a powerful tool for neuronal disruption.

  • Behavioral Effect of chemogenetic inhibition is directly related to receptor transduction levels in rhesus monkeys
    2018
    Co-Authors: Nicholas A. Upright, Stephen W. Brookshire, Wendy Schnebelen, Christienne G. Damatac, Patrick R. Hof, Philip G. F. Browning, Paula L. Croxson, Peter H. Rudebeck, Mark G. Baxter
    Abstract:

    We used inhibitory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) to reversibly disrupt dorsolateral prefrontal cortex (dlPFC) function in male macaque monkeys. Monkeys were tested on a spatial delayed response task to assess working memory function after intramuscular injection of either clozapine-N-oxide (CNO) or vehicle. CNO injections given before DREADD transduction were without Effect on behavior. rAAV5/hsyn-hM4Di-mCherry was injected bilaterally into the dlPFC of five male rhesus monkeys, to produce neuronal expression of the inhibitory (Gi-coupled) DREADD receptor. We quantified the percentage of DREADD-transduced cells using stereological analysis of mCherry-immunolabeled cells. We found a greater number of immunolabeled neurons in monkeys that displayed CNO-induced Behavioral impairment after DREADD transduction compared to monkeys that showed no Behavioral Effect after CNO. Even in monkeys that showed reliable Effects of CNO on behavior after DREADD transduction, the number of prefrontal neurons transduced with DREADD receptor was on the order of 3% of total prefrontal neurons counted. This level of histological analysis facilitates our understanding of Behavioral Effects, or lack thereof, after DREADD vector injection in monkeys. It also implies that a functional silencing of a relatively small fraction of dlPFC neurons, albeit in a widely distributed area, is sufficient to disrupt spatial working memory.

Jacques Balthazart - One of the best experts on this subject based on the ideXlab platform.

  • estradiol rapidly activates male sexual behavior and affects brain monoamine levels in the quail brain
    Behavioural Brain Research, 2006
    Co-Authors: Christina Dalla, Z Papadopouloudaifoti, Michelle Baillien, Charlotte A Cornil, Jacques Balthazart
    Abstract:

    Abstract Steroids are generally viewed as transcription factors binding to intracellular receptors and activating gene transcription. Rapid cellular Effects mediated via non-genomic mechanisms have however been identified and one report showed that injections of estradiol rapidly stimulate chemoinvestigation and mounting behavior in castrated male rats. It is not known whether such Effects take place in other species and what are the cellular underlying mechanisms. We show here that a single injection of estradiol (500 μg/kg) rapidly and transiently activates copulatory behavior in castrated male quail pre-treated with a dose of testosterone Behaviorally inEffective by itself. The maximal Behavioral Effect was observed after 15 min. In a second experiment, the brain of all subjects was immediately collected after Behavioral tests performed 15 min after injection. The preoptic area—hypothalamus (HPOA), hindbrain, telencephalon and cerebellum were isolated and monoamines measured by HPLC-ED. Estradiol increased levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/serotonin ratios in the telencephalon and hindbrain independently of whether animals had mated or not. Estradiol also affected these measures in HPOA and cerebellum but this Effect was correlated with the level of sexual activity so that significant Effects of the treatment only appeared when sexual activity was used as a covariate. Interactions between estradiol Effects and sexual activity were also observed for dopamine in the HPOA and for serotonin in the hindbrain and cerebellum. Together, these data demonstrate that a single estradiol injection rapidly activates male sexual behavior in quail and that this Behavioral Effect is correlated with changes in monoaminergic activity.

Richard J Beninger - One of the best experts on this subject based on the ideXlab platform.

  • increased drinking following social isolation rearing implications for polydipsia associated with schizophrenia
    PLOS ONE, 2013
    Co-Authors: Emily R Hawken, Nicholas J Delva, Richard J Beninger
    Abstract:

    Primary polydipsia, excessive drinking without known medical cause, is especially associated with a diagnosis of schizophrenia. We used animal models of schizophrenia-like symptoms to examine the Effects on schedule-induced polydipsia: post-weaning social isolation rearing, subchronic MK-801 treatment (an NMDA-receptor antagonist) or the two combined. Male, Sprague-Dawley rats reared in groups or in isolation beginning at postnatal day 21 were further divided to receive subchronic MK-801 (0.5 mg/kg twice daily) or saline for 7 days beginning on postnatal day 62. Following a 4-day withdrawal period, all groups were trained on a schedule-induced polydipsia paradigm. Under food-restriction, animals reared in isolation and receiving food pellets at 1-min intervals developed significantly more drinking behavior than those reared with others. The addition of subchronic MK-801 treatment did not significantly augment the amount of water consumed. These findings suggest a predisposition to polydipsia is a schizophrenia-like Behavioral Effect of post-weaning social isolation.

Toshihiro Sugiyama - One of the best experts on this subject based on the ideXlab platform.

  • Fragment of human beta-fibrinogen induces a Behavioral Effect on mouse forced swimming.
    Peptides, 2002
    Co-Authors: Yutaka Masuda, Yoshihiko Kawarada, Shun Ohunuma, Junya Sugawara, Toshihiro Sugiyama
    Abstract:

    Abstract We detected a peptide having a Behavioral activity on mouse forced swimming from sera of healthy volunteers without affective and psychotic diseases. The amino acid sequence was GVNDNEEGF, which was found in the sequence of human β-fibrinogen. The synthesized peptide also showed the Behavioral activity dose-dependently, but human fibrinopeptide B (QGVDNEEGFFSAR) did not. The activity was decreased by dopamine 1 antagonist SCH-23390, but not by dopamine 2 antagonist sulpiride. These findings strongly suggest that metabolism of human β-fibrinogen induces the fragment affecting the mouse behavior via the dopamine1 neuronal activity.

  • Behavioral Effect of herbal glycoside in the forced swimming test.
    Methods and Findings in Experimental and Clinical Pharmacology, 2002
    Co-Authors: Yutaka Masuda, Ohnuma S, Sugawara J, Kawarada Y, Toshihiro Sugiyama
    Abstract:

    We investigated the Behavioral Effects of Chinese herbal medicines in the forced swimming test. One of these medicines, Kami-shoyo-san, induced an antidepressive climbing behavior in mice. An Effective substance detected to be an O-linked glycoside with the sugar chain structure GalNAc alpha 1-3GalNAc was separated. The Behavioral Effect was dose-dependently decreased by the dopamine 2 antagonist sulpiride, but not by the dopamine 1 antagonist SCH-233960. Investigated Chinese herbal medicines, including Kami-shoyo-san, have been used for human depression. These facts suggest that glycoside is one of the antidepressant-like substances of Chinese herbal medicines.

  • Behavioral Effect of mouse fibrinopeptide a on mouse forced swimming
    Peptides, 2000
    Co-Authors: Yutaka Masuda, Yoshihiko Kawarada, Toshihiro Sugiyama
    Abstract:

    Abstract A specific dopamine 2 receptor antagonist, (−)sulpiride, induced an anti-depressive behavior, climbing, in mice forced to swim for 6 h after the injection. The Effective fraction was divided from the mouse serum using an ion exchanger and an ultra filtration method. This fraction contained fibrinopeptide A. A peptide synthesized according to the primary 6-amino acid sequence (TDTEDK) of fibrinopeptide A also remarkably increased the behavior. The present findings clearly indicate that a peptide with TDTEDK showed anti-depressive activity.