FLUOXETINE-INDUCED DESENSITIZATION OF SOMATODENDRITIC 5-HT1A AUTORECEPTORS IS INDEPENDENT OF GLUCOCORTICOID(S)

Previous in vitro studies showed that glucocorticoid receptor activati on (notably by corticosterone) could induce a functional desensitizati on of somatodendritic 5-HT1A autoreceptors in the dorsal raphe nucleus [Laaris et al. (1995) Neuropharmacology 34:1201-1210], similar to tha t due to in vivo subchronic treatment with a 5-HT reuptake inhibitor, such as fluoxetine, in rats. In the present study, we investigated whe ther a link might exist between these effects, i.e., whether glucocort icoid receptor activation could be responsible for the fluoxetine-indu ced desensitization of 5-HT1A autoreceptors. In vitro recording in the dorsal raphe nucleus of brain-stem slices showed that subchronic trea tment with fluoxetine (5 mg/kg intraperitoneally (i.p.), daily for 3-7 days) significantly reduced the potency of the 5-HT1A receptor agonis t ipsapirone to inhibit the firing rate of serotoninergic neurons. Par allel experiments in adrenalectomized and sham-operated rats indicated that subchronic fluoxetine treatment produced a similar shift to the right of the ipsapirone inhibition curve in both groups of animals. Fu rthermore, the subchronic blockade of glucocorticoid receptors by RU 3 8486 (25 mg/kg subcutaneously (s.c.), daily) in intact rats treated wi th fluoxetine (5 mg/kg i.p., daily for 3 days) did not affect the abil ity of the latter treatment to reduce the potency of ipsapirone to inh ibit the firing of serotoninergic neurons. These data suggest that glu cocorticoid receptors (and their possible activation by corticosterone ) are not involved in the functional desensitization of somatodendriti c 5-HT1A autoreceptors, which occurs during long-term treatment with a serotonin reuptake inhibitor such as fluoxetine. (C) 1997 Wiley-Liss, Inc.