EFFECT OF ACUTE AND CHRONIC FLUOXETINE ON EXTRACELLULAR DOPAMINE LEVELS IN THE CAUDATE-PUTAMEN AND NUCLEUS-ACCUMBENS OF RAT

Recent studies indicate that an increase in serotonergic (5-HT) activi ty in the nucleus accumbens (NAc) produces an increase in dopamine (DA ) release, providing a possible mechanism for the involvement of DA in the therapeutic action of selective serotonin reuptake inhibitor (SSR I) antidepressants. However, acutely administered fluoxetine (2.5, 5.0 , or 10.0 mg/kg, i.p.) failed to elevate extracellular levels of DA, o r its metabolites in the NAc or caudate-putamen (CP). In fact, the hig hest dose produced a small (20%) decrease in DA levels in the NAc. Ext racellular levels of the 5-HT metabolite 5HIAA were consistently decre ased at all doses of fluoxetine in both structures. Since SSRIs genera lly require several weeks of treatment to be effective clinically, a s econd experiment examined the effect of chronic administration of fluo xetine. Chronic (21 day) daily treatment with 5 mg/kg had no effect on NAc basal levels of DA, DA metabolites, or 5HIAA, relative to a salin e-treated control group. Finally, pretreatment with fluoxetine appeare d to slightly enhance the elevation of NAc DA induced by an injection of cocaine (10 mg/kg, i.p.), an effect that was not quite significant (P < .06). In conclusion, the 5-HT-induced facilitation of NAc DA neur otransmission described in the literature may not be relevant to the t herapeutic action of fluoxetine. (C) 1996 Wiley-Liss, Inc.