5HT2C receptor agonists and antagonists in animal models of anxiety
摘要
The diverse effects of serotonin (5HT) are mediated by a variety of 5HT receptor subtypes. Due to their relative brain specificity and pattern of regional mRNA distribution, 5HT2C receptors offer a promising target for designing novel drugs for the therapy of neuropsychiatric disorders in which serotonergic neurotransmission plays an important role. Accumulating evidence suggests that 5-HT2C receptor-mediated functions may share involvement in the clinical efficacy of a number of marketed drugs (e.g., Jenck et al., 1993). Chronic exposure of rats to unpredictable mild stressors, a procedure known to induce anhedonia (“depression-like syndrome”) in animals and man, facilitated 5-HT2C receptor function, whereas antidepressant treatments did the opposite (Moreau et al., 1993). Preclinical support for possible involvement of 5HT2C receptors in anxiety is provided by demonstration of anxiolytic-like effects of 5HT2C/2B receptor antagonist SB200646A and of 5HT2A/2C receptor antagonist mianserin, but not of 5HT2A receptor antagonist ketanserin (cf. Kennett et al., 1994). The present study characterized selected 5HT2C receptor ligands (agonists, partial agonist, antagonist) in several animal models of anxiety disorders.