AUTORECEPTOR ANTAGONISTS ENHANCE THE EFFECT OF THE REUPTAKE INHIBITORCITALOPRAM ON EXTRACELLULAR 5-HT - THIS EFFECT PERSISTS AFTER REPEATED CITALOPRAM TREATMENT

The effect of repeated administration of the reuptake inhibitor citalo pram (10 mg/kg s.c., b.i.d. for 14 days) or saline on extracellular 5- hydroxytryptamine (5-HT) and autoreceptor sensitivity was assessed usi ng microdialysis in the frontal cortex (FCx) and dorsal hippocampus (D H) of unanesthetized rats. Acute citalopram (5 mg/kg s.c.) challenge p roduced significant increases in DH and FCx 5-HT. The nonselective 5-H T1A/1B receptor antagonist (-)-penbutolol (8 mg/kg s.c.), administered 2 hr after citalopram challenge, significantly enhanced 5-HT in FCx a nd DH of both the chronic citalopram and saline pretreatment groups. A dministration of the selective 5-HT1A receptor antagonist WAY100635 (0 .3 mg/kg s.c.) after citalopram challenge significantly enhanced 5-HT in FCx but not DH of both pretreatment groups. This suggests that ther e may be differences between DH and FCx in regulation of 5-HT release. Nevertheless, these results provide evidence that 5-HT autoreceptors are still active in restraining 5-HT release even after repeated admin istration of an antidepressant drug. (C) 1997 Elsevier Science Ltd.