Involvement of 5-HT2C and 5-HT1A receptors of the basolateral nucleus of the amygdala in the anxiolytic effect of chronic antidepressant treatment

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.