Dopamine D3-Like Receptors Modulate Anxiety-Like Behavior and Regulate GABAergic Transmission in the Rat Lateral/Basolateral Amygdala

Central among the brain regions that regulate fear/anxiety behaviors is the lateral/basolateral amygdala (BLA). BLA output is tightly controlled by the relative activity of two populations of inhibitory GABAergic interneurons, local feedback cells distributed throughout the nucleus, and feedforward cells found along the lateral paracapsular border of this subdivision. Recent studies suggest that dopamine (DA) can modulate the BLA GABAergic system, thus linking fear/anxiety states with mesolimbic reward/attentional processes. However, the precise dopaminergic mechanisms regulating the activity of the two BLA GABAergic neuron populations have not been fully explored. We therefore examined the effects of DA D3-like receptors on BLA-dependent anxiety-like behavior and neurophysiology. After confirming the presence of D3-like receptors within the BLA, we found that microinjection of a D3-selective antagonist into the BLA decreased anxiety-like behavior expressed in both the light/dark transition test and the elevated plus maze. Consistent with this, we found that in vitro D3-like receptor activation selectively inhibits synaptic transmission at both BLA feedback and feedforward GABAergic interneuron populations, with no effect on glutamatergic transmission. This inhibition of GABAergic transmission is a result of a D3-like receptor-mediated, dynamin-dependent process that presumably reflects endocytosis of postsynaptic GABAA receptors found on principal BLA neurons. Because environmental cues alter both DA release and relative activity states of the BLA, our data strongly suggest that DA, potentially acting through D3-like receptors, may suppress the relative contribution by inhibitory processes in the BLA and modify the expression of BLA-related behaviors

Activation of Group II Metabotropic Glutamate Receptors Inhibits the Discriminative Stimulus Effects of Alcohol via Selective Activity Within the Amygdala

Metabotropic glutamate receptor subtypes (mGlu2/3) regulate a variety of alcohol-associated behaviors, including alcohol reinforcement, and relapse-like behavior. To date, the role of mGlu2/3 receptors in modulating the discriminative stimulus effects of alcohol has not been examined. Given that the discriminative stimulus effects of drugs are determinants of abuse liability and can influence drug seeking, we examined the contributions of mGlu2/3 receptors in modulating the discriminative stimulus effects of alcohol. In male Long-Evans rats trained to discriminate between alcohol (1 g/kg, IG) and water, the mGlu2/3 agonist LY379268 (0.3–10 mg/kg) did not produce alcohol-like stimulus effects. However, pretreatment with LY379268 (1 and 3 mg/kg; in combination with alcohol) inhibited the stimulus effects of alcohol (1 g/kg). Systemic LY379268 (3 mg/kg, i.p.) was associated with increases in neuronal activity within the amygdala, but not the nucleus accumbens, as assessed by c-Fos immunoreactivity. Intra-amygdala activation of mGlu2/3 receptors by LY379268 (6 μg) inhibited the discriminative stimulus effects of alcohol, without altering response rate. In contrast, intra-accumbens LY379268 (3 μg) profoundly reduced response rate; however, at lower LY379268 doses (0.3, 1 μg), the discriminative stimulus effects of alcohol and response rate were not altered. These data suggest that amygdala mGlu2/3 receptors have a functional role in modulating the discriminative stimulus properties of alcohol and demonstrate differential motor sensitivity to activation of mGlu2/3 receptors in the amygdala and the accumbens. Understanding the neuronal mechanisms that underlie the discriminative stimulus effects of alcohol may prove to be important for future development of pharmacotherapies for treating alcoholism

Post‐HCV cure self‐reported changes in physical activity, eating behaviours, and fatigue in people living with HIV (ANRS CO13 HEPAVIH)

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Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients: A Longitudinal Analysis (ANRS CO13 HEPAVIH)

International audienceDiabetes and insulin resistance (IR) is common in human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients, a population also concerned with elevated cannabis use. Cannabis has been associated with reduced IR risk in some population-based surveys. We determined whether cannabis use was consistently associated with reduced IR risk in HEPAVIH, a French nationwide cohort of HIV-HCV-coinfected patients.Methods: HEPAVIH medical and sociobehavioral data were collected (using annual self-administered questionnaires). We used 60 months of follow-up data for patients with at least 1 medical visit where IR (using homeostatic model assessment of insulin resistance [HOMA-IR]) and cannabis use were assessed. A mixed logistic regression model was used to evaluate the association between IR risk (HOMA-IR > 2.77) and cannabis use (occasional, regular, daily).Results: Among the 703 patients included in the study (1287 visits), 323 (46%) had HOMA-IR > 2.77 for at least 1 follow-up visit and 319 (45%) reported cannabis use in the 6 months before the first available visit. Cannabis users (irrespective of frequency) were less likely to have HOMA-IR > 2.77 (odds ratio [95% confidence interval], 0.4 [.2-.5]) after adjustment for known correlates/confounders. Two sensitivity analyses with HOMA-IR values as a continuous variable and a cutoff value of 3.8 confirmed the association between reduced IR risk and cannabis use.Conclusions: Cannabis use is associated with a lower IR risk in HIV-HCV-coinfected patients. The benefits of cannabis-based pharmacotherapies for patients concerned with increased risk of IR and diabetes need to be evaluated in clinical research and practice