Psychopharmacology
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Administration of 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptor agonists into the dorsal periaqueductal gray (DPAG) inhibits escape, a defensive behavior associated with panic attacks. Long-term treatment with the antipanic compound imipramine enhances the DPAG 5-HT1A- and 5-HT2A-receptor-mediated inhibition of escape, implicating these receptors in the mode of action of panicolytic drugs. ⋯ The results suggest that facilitation of the 5-HT1A- and 5-HT2A-receptor-mediated inhibition of DPAG neuronal activity is implicated in the beneficial effect of antidepressants in panic disorder.
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In previous drug discrimination studies we observed surmountable antagonism by Delta(9)-tetrahydrocannabinol (THC) in the presence of constant doses of SR-141716 [N-(piperidin-1-yl)-5-(4-chloro-phenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] (0.3 and 1 mg/kg), but there was only marginal evidence for surmountable antagonism with combinations of SR-141716 and (R)-methanandamide, a chiral analog of the endocannabioid anandamide. ⋯ Data support that the discriminative stimulus effects of (R)-methanandamide and its overlap with the Delta(9)-THC cue are, indeed, CB1 receptor mediated events as revealed in antagonism tests with the selective central CB1 receptor antagonists SR-141716 and AM-251. The activation of cannabinoid CB2 receptors appears to be insignificant for these discriminations.