title: Involvement of 5-HT2C and 5-HT1A receptors of the basolateral nucleus of the amygdala in the anxiolytic effect of chronic antidepressant treatment.
abstract: Facilitation of serotonin 2C- and 1A-receptor (5-HT2C-R and 5-HT1A-R) mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) has been associated with anxiogenic and anxiolytic effects, respectively. It has been also shown that stimulation of BLA 5-HT2C-Rs underlies the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine or fluoxetine. Here we investigated whether chronic treatment with these two antidepressants, which causes anxiolytic effects, decreases the responsiveness of these receptors in the BLA. We also investigated whether the blockage of 5-HT1A-Rs in the same amygdala nucleus alters the anxiolytic effect of chronic imipramine treatment. The results showed that in male Wistar rats intra-BLA injection of the 5-HT2C-R agonist MK-212 facilitated inhibitory avoidance acquisition in the elevated T-maze and decreased the percentage of time spent by the animals in the lit compartment of the light-dark transition test, indicating an anxiogenic effect. Chronic (21 days) systemic treatment with imipramine (5 or 15 mg/kg) or fluoxetine (10 mg/kg) abolished these effects of MK-212. Acute administration of imipramine (5 mg/kg) failed to interfere with MK-212 effects in both tests. Intra-BLA injection of the 5-HT1A antagonist WAY-100635 blocked the anxiolytic, but not the panicolytic, effect of imipramine in the tests used. Our findings indicate that both a reduction in 5-HT2C-R- and a facilitation of 5-HT1A-R-mediated neurotransmission in the BLA are involved in the anxiolytic effect of antidepressant drugs.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Maria Adrielle
authors.initials: MA
authors.lastname: Vicente
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil. Electronic address: zangross@fmrp.usp.br.
authors.forename: Helio
authors.initials: H
authors.lastname: Zangrossi
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D010200:Panic / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D010879:Piperazines; D011719:Pyrazines; D011725:Pyridines; D044405:Receptor, Serotonin, 5-HT2C; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; C014896:6-chloro-2-(1-piperazinyl)pyrazine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D007099:Imipramine
keywords: 5-HT2C receptors; Antidepressants and basolateral amygdala; Anxiety; Serotonin