Anxiety disorders are among the most prevalent categories of mental illnesses. The gut-brain axis... more Anxiety disorders are among the most prevalent categories of mental illnesses. The gut-brain axis, along with gastrointestinally-derived neuropeptides, like glucagon-like peptide-1 (GLP-1), are emerging as potential key regulators of emotionality, including anxiety behavior. However, the neuroanatomical substrates from which GLP-1 exerts its anxiogenic effect remain poorly characterized. Here we focus on a relatively new candidate nucleus, the supramammillary nucleus (SuM), located just caudal to the lateral hypothalamus and ventral to the ventral tegmental area. Our focus on the SuM is supported by previous data showing expression of GLP-1R mRNA throughout the SuM and activation of the SuM during anxiety-inducing behaviors in rodents. Data show that chemogenetic activation of neurons in the SuM results in an anxiolytic response in male and female rats. In contrast, selective activation of SuM GLP-1R, by microinjection of a GLP-1R agonist exendin-4 into the SuM resulted in potent anxiety-like behavior, measured in both open field and elevated plus maze tests in male and female rats. This anxiogenic effect of GLP-1R activation persisted after high-fat diet exposure. Importantly, reduction of GLP-1R expression in the SuM, by AAV-shRNA GLP-1R knockdown, resulted in a clear anxiolytic response; an effect only observed in female rats. Our data identify a new neural substrate for GLP-1 control of anxiety-like behavior and indicate that the SuM GLP-1R are sufficient for anxiogenesis in both sexes, but necessary only in females.
There is a substantial need for new pharmacological treatments of addiction, and appetite-regulat... more There is a substantial need for new pharmacological treatments of addiction, and appetite-regulatory peptides are implied as possible candidates. Appetite regulation is complex and involves anorexigenic hormones such as glucagon-like peptide-1 (GLP-1) and amylin, and orexigenic peptides like ghrelin and all are well-known for their effects on feeding behaviors. This overview will summarize more recent physiological aspects of these peptides, demonstrating that they modulate various aspects of addiction processes. Findings from preclinical, genetic, and experimental clinical studies exploring the association between appetite-regulatory peptides and the acute or chronic effects of addictive drugs will be introduced. Short or long-acting GLP-1 receptor agonists independently attenuate the acute rewarding properties of addictive drugs or reduce the chronic aspects of drugs. Genetic variation of the GLP-1 system is associated with alcohol use disorder. Also, the amylin pathway modulates ...
Testosterone plays a key role in the control of seasonal changes in singing behavior and its unde... more Testosterone plays a key role in the control of seasonal changes in singing behavior and its underlying neural circuitry. After administration of exogenous testosterone, song quality and song control nuclei volumes change over the course of weeks, but song rate increases within days. The medial preoptic nucleus (POM) controls sexual motivation and testosterone action in POM increases sexually motivated singing. Here, we investigated the time course of testosterone action in the song control nuclei and POM, at the gross anatomical and cellular level. Photosensitive female canaries were injected with BrdU to label newborn neurons. One day later they were transferred to a long day photoperiod and implanted with testosterone-filled or empty implants. Brains and blood were collected 1, 2, 9 or 21 days later. Testosterone increased POM volume within one day, whereas the volume of song control nuclei increased significantly only on day 21 even if a trend was already observed for HVC on day...
Journal of the experimental analysis of behavior, 2018
In two experiments, experimentally naïve rats were trained in concurrent variable-interval schedu... more In two experiments, experimentally naïve rats were trained in concurrent variable-interval schedules in which the reinforcer ratios changed daily according to a pseudorandom binary sequence. In Experiment 1, relative response rates showed clear sensitivity to current-session reinforcer ratios, but not to previous sessions' reinforcer ratios. Within sessions, sensitivity to the current session's reinforcement rates increased steadily, and by session end, response ratios approached matching to the current-session reinforcer ratios. Across sessions, sensitivity to the current session's reinforcer ratio decreased with continued exposure to the pseudorandom binary sequence, contrary to expectations based on previous studies demonstrating learning sets. Using a second group of naïve rats, Experiment 2 replicated the main results from Experiment 1 and showed that although there were increases over sessions in both changeover rate and response rate during the changeover delay, n...
Anxiety disorders are among the most prevalent categories of mental illnesses. The gut-brain axis... more Anxiety disorders are among the most prevalent categories of mental illnesses. The gut-brain axis, along with gastrointestinally-derived neuropeptides, like glucagon-like peptide-1 (GLP-1), are emerging as potential key regulators of emotionality, including anxiety behavior. However, the neuroanatomical substrates from which GLP-1 exerts its anxiogenic effect remain poorly characterized. Here we focus on a relatively new candidate nucleus, the supramammillary nucleus (SuM), located just caudal to the lateral hypothalamus and ventral to the ventral tegmental area. Our focus on the SuM is supported by previous data showing expression of GLP-1R mRNA throughout the SuM and activation of the SuM during anxiety-inducing behaviors in rodents. Data show that chemogenetic activation of neurons in the SuM results in an anxiolytic response in male and female rats. In contrast, selective activation of SuM GLP-1R, by microinjection of a GLP-1R agonist exendin-4 into the SuM resulted in potent anxiety-like behavior, measured in both open field and elevated plus maze tests in male and female rats. This anxiogenic effect of GLP-1R activation persisted after high-fat diet exposure. Importantly, reduction of GLP-1R expression in the SuM, by AAV-shRNA GLP-1R knockdown, resulted in a clear anxiolytic response; an effect only observed in female rats. Our data identify a new neural substrate for GLP-1 control of anxiety-like behavior and indicate that the SuM GLP-1R are sufficient for anxiogenesis in both sexes, but necessary only in females.
There is a substantial need for new pharmacological treatments of addiction, and appetite-regulat... more There is a substantial need for new pharmacological treatments of addiction, and appetite-regulatory peptides are implied as possible candidates. Appetite regulation is complex and involves anorexigenic hormones such as glucagon-like peptide-1 (GLP-1) and amylin, and orexigenic peptides like ghrelin and all are well-known for their effects on feeding behaviors. This overview will summarize more recent physiological aspects of these peptides, demonstrating that they modulate various aspects of addiction processes. Findings from preclinical, genetic, and experimental clinical studies exploring the association between appetite-regulatory peptides and the acute or chronic effects of addictive drugs will be introduced. Short or long-acting GLP-1 receptor agonists independently attenuate the acute rewarding properties of addictive drugs or reduce the chronic aspects of drugs. Genetic variation of the GLP-1 system is associated with alcohol use disorder. Also, the amylin pathway modulates ...
Testosterone plays a key role in the control of seasonal changes in singing behavior and its unde... more Testosterone plays a key role in the control of seasonal changes in singing behavior and its underlying neural circuitry. After administration of exogenous testosterone, song quality and song control nuclei volumes change over the course of weeks, but song rate increases within days. The medial preoptic nucleus (POM) controls sexual motivation and testosterone action in POM increases sexually motivated singing. Here, we investigated the time course of testosterone action in the song control nuclei and POM, at the gross anatomical and cellular level. Photosensitive female canaries were injected with BrdU to label newborn neurons. One day later they were transferred to a long day photoperiod and implanted with testosterone-filled or empty implants. Brains and blood were collected 1, 2, 9 or 21 days later. Testosterone increased POM volume within one day, whereas the volume of song control nuclei increased significantly only on day 21 even if a trend was already observed for HVC on day...
Journal of the experimental analysis of behavior, 2018
In two experiments, experimentally naïve rats were trained in concurrent variable-interval schedu... more In two experiments, experimentally naïve rats were trained in concurrent variable-interval schedules in which the reinforcer ratios changed daily according to a pseudorandom binary sequence. In Experiment 1, relative response rates showed clear sensitivity to current-session reinforcer ratios, but not to previous sessions' reinforcer ratios. Within sessions, sensitivity to the current session's reinforcement rates increased steadily, and by session end, response ratios approached matching to the current-session reinforcer ratios. Across sessions, sensitivity to the current session's reinforcer ratio decreased with continued exposure to the pseudorandom binary sequence, contrary to expectations based on previous studies demonstrating learning sets. Using a second group of naïve rats, Experiment 2 replicated the main results from Experiment 1 and showed that although there were increases over sessions in both changeover rate and response rate during the changeover delay, n...
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Papers by Olesya Shevchouk