ROLE OF CENTRAL SEROTONERGIC NEURONS IN THE EFFECT OF SERTRALINE IN RATS IN THE FORCED SWIMMING TEST

Sertraline, administered i.p. in single doses or as three injections in 24 h, significantly reduced the immobility of rats in the forced swimming test at 64 and 100-mu-mol/kg. The effect of three doses of 64-mu-mol/kg in 24 h was not modified in animals treated i.p. with metergoline (5 mg/kg) 3 h before testing. I.c.v. administration of 150-mu-g 5,7-dihydroxytryptamine, which depleted brain serotonin, or infusion of 6-mu-g 6-hydroxydopamine in the locus coeruleus, which markedly depleted noradrenaline in terminal regions, was also ineffective. The effect of 64-mu-mol/kg sertraline, once daily for 7 days, was not modified by i.c.v. 5,7-dihydroxytryptamine. The effect of three doses of 64-mu-mol/kg sertraline in 24 h was instead completely antagonized by 100 mg/kg sulpiride given 90 min before testing. The exact mechanism of this effect and its relevance for the favourable effects of sertraline in human depression remain to be clarified.