Chronic administration of the 5-HT1A receptor agonist 8-OH-DPAT differentially desensitizes 5-HT1A autoreceptors of the dorsal and median raphe nuclei.

The present study investigated alterations of the regulation of serotonin (5-hydroxytryptamine; 5-HT) release by 5-HT1A autoreceptors following single and repeated treatment with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT). Rats were pretreated with 8-OH-DPAT (1.0 mg/kg, s.c.) for 1, 7, or 14 days. The ability of an acute challenge administration of 8-OH-DPAT (1.0 mg/kg, i.p.) to decrease 5-HT release in the ventral striatum and the ventral hippocampus of rats maintained under chloral hydrate anesthesia was examined 24 h after the last pretreatment injection using in vivo microdialysis. The decrease of 5-HT release in the striatum produced by the challenge dose of the 5-HT1A receptor agonist was diminished following 7 and 14 days of pretreatment, but not after 1 day of pretreatment, with 8-OH-DPAT. In contrast, decreases of 5-HT release in the hippocampus by the 8-OH-DPAT challenge were not altered after 1 or 7 days of pretreatment, and only a trend for attenuation appeared after pretreatment for 14 days. The results of the present study indicate that desensitization of 5-HT1A autoreceptors regulating 5-HT release in different brain regions by repeated treatment with 8-OH-DPAT occurs at different rates.