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The effects of acute (1 hr) and chronic (21 days) treatment with the antidepressant drug citalopram (5-HT reuptake inhibitor) on 5-HT function in frontal cortex of the rat were studied by monitoring the serotonergic inactivation of adenylyl cyclase (AC) and the 5-HT1A autoreceptor-mediated inhibition of [3H] 5-HT release and uptake. Acute treatment (1.25-10 mg/kg i.p.) with citalopram produced a dose-dependent decrease in the number of [3H] 5-HT binding sites with no change in affinity. These effects were found to be selective since no changes in the binding parameters of [3H]GBR 12935 (a 5-HT1A agonist) were observed. Chronic (10-20 mg/kg i.p.) citalopram treatment did not alter the density of [3H] 5-HT binding sites, but increased the potency and maximal inhibitory effect of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin. In contrast, the potency and maximal inhibitory effect of the 5-HT releaser, N-allylnormetazocine (SKF 38393), was significantly reduced by chronic treatment. Citalopram (10-20 mg/kg i.p.) did not alter the sensitivity or maximal effect of a high dose (50 nM) of the direct 5-HT agonist quipazine, but decreased the potency of N-allylnormetazocine without altering its maximal inhibitory effect. A chronic treatment with citalopram also significantly decreased the potency of several 5-HT1A agonists, including 8 0b46394aab
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