Chronic fluoxetine treatment up‐regulates dopamine receptors in the mesolimbic forebrain of the rat

The mechanism of antidepressant function is still largely unknown. The authors examined the binding of [H] SCH 23390 and [³H] spiperone to dopantine D₁‐ and D₂‐like receptors, respectively, using quantitative in vitro receptor autoradiogra‐phy inforebrain sections front rats treated for 8 weeks with 5 mg/kg fluoxetine HCl or vehicle. Fluoxetine treatment significantly increased dopamine D₁ receptor density in the nucleus accumbens and D₂ density in the nucleus accumbens, olfactory tubercle and islands of Calleja region. Neither D₁ nor D₂ receptors were significantly affected in the striatum. The results are discussed in light of additional evidence that antidepressants alter mesolimbic dopamine function. Although fluoxetine (Prozac) selectively inhibits reuptake of serotonin, its indirect effects on mesolimbic dopamine systems might underlie its potent efficacy as an antidepressant. Depression 1:82–87 (1993). © 1993 Wiley‐Liss, Inc.