title: Regulation of rat cortical 5-hydroxytryptamine2A receptor-mediated electrophysiological responses by repeated daily treatment with electroconvulsive shock or imipramine.
abstract: Down-regulation of 5-hydroxytryptamine(2A) (5-HT(2A)) receptors has been a consistent effect induced by most antidepressant drugs. In contrast, electroconvulsive shock (ECS) up-regulates the number of 5-HT(2A) receptor binding sites. However, the effects of antidepressants on 5-HT(2A) receptor-mediated responses on identified cells of the cerebral cortex have not been examined. The purpose of the present study was to compare the effects of the tricyclic antidepressant imipramine and ECS on 5-HT(2A) receptor-mediated electrophysiological responses involving glutamatergic and GABAergic neurotransmission in the rat medial prefrontal cortex (mPFC) and piriform cortex, respectively. The electrophysiological effects of activating 5-HT(2A) receptors were consistent with 5-HT(2A) receptor binding regulation for imipramine and ECS except for the mPFC where chronic ECS decreased the potency of 5-HT at a 5-HT(2A) receptor-mediated response. These findings are consistent with the general hypothesis that chronic antidepressant treatments shift the balance of serotonergic neurotransmission towards inhibitory effects in the cortex.
authors.affiliation: Discovery Biology, Eli Lilly Corporate Center, Mail Drop 0510, Indianapolis, IN 46285, United States. gerard_j_marek@lilly.com
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Marek
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000379:methods*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D000929:Antidepressive Agents, Tricyclic; D018690:Excitatory Amino Acid Agonists; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007099:Imipramine