Differential regulation of serotonin (5-HT) release in the striatum and hippocampus by 5-HT(1A) autoreceptors of the dorsal and median raphe nuclei

The present study characterized the pharmacological mechanisms and regional selectivity of the regulation of serotonin (5-HT) release by 5- HT(1A) autoreceptors. 5-HT release was measured simultaneously in the striatum and ventral hippocampus by using in vivo microdialysis in rats maintained under chloral hydrate anesthesia. Systemic administration of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) produced complete reductions of 5-HT release. The effects of systemic 8-OH- DPAT on 5-HT release were blocked completely by systemic administration of the 5-HT/beta adrenergic receptor antagonist, (-)-propranolol, but not by the beta-1 adrenergic receptor antagonist betaxolol or the beta-2 adrenergic receptor antagonist ICI-118,551. Local administration of 8-OH-DPAT into the striatum or hippocampus through the microdialysis probe did not alter 5-HT release. Local administration of 8-OH-DPAT into the dorsal raphe nucleus reduced 5-HT release in the striatum, but not in the hippocampus. Conversely, administration of 8-OH-DPAT into the median raphe nucleus reduced 5-HT release in the hippocampus, but not in the striatum. The effects of systemic 8-OH-DPAT on striatal 5-HT release were selectively blocked by concurrent administration of (-)-propranolol into the dorsal raphe nucleus, whereas effects of systemic 8-OH-DPAT on hippocampal 5-HT release were selectively blocked by concurrent administration of (-)-propranolol into the median raphe nucleus. The present study suggests that somatodendritic 5-HT(1A) receptors regulate the release of 5-HT in a regionally dependent manner.