Effect of acute and chronic fluoxetine on extracellular dopamine levels in the caudate-putamen and nucleus accumbens of rat

✍ Scribed by Robert N. Clark; Charles R. Ashby Jr.; Stephen L. Dewey; P. Veeraraghavan Ramachandran; Robert E. Strecker

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 710 KB
• Volume: 23
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199607)23:3<125::aid-syn1>3.0.co;2-a

✦ Synopsis

Recent studies indicate that an increase in serotonergic (5-HT) activity 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 (SSRI) antidepressants. However, acutely administered fluoxetine (2.5, 5.0, or 10.0 mgkg, i.p.1 failed to elevate extracellular levels of DA, or its metabolites in the NAc or caudate-putamen (CP). In fact, the highest dose produced a small (20%) decrease in DA levels in the NAc. Extracellular levels of the 5-HT metabolite 5HIAA were consistently decreased at all doses of fluoxetine in both structures. Since SSRIs generally require several weeks of treatment to be effective clinically, a second experiment examined the effect of chronic administration of fluoxetine. Chronic (21 day) daily treatment with 5 mgkg had no effect on NAc basal levels of DA, DA metabolites, or 5HIAA, relative to a saline-treated control group. Finally, pretreatment with fluoxetine appeared to slightly enhance the elevation of NAc DA induced by an injection of cocaine (10 mgkg, i.p.), an effect that was not quite significant (P < .06). In conclusion, the 5-HT-induced facilitation of NAc DA neurotransmission described in the literature may not be relevant to the therapeutic action of fluoxetine. o 1996 Wiley-Liss, Inc.