Differential regulation of serotonin (5-HT) release in the striatum and hippocampus by 5-HT1A 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-HT1A 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-HT1A 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-HT1A receptors regulate the release of 5-HT in a regionally dependent manner.
Department of Psychiatry, University of Pennsylvania, Philadelphia.
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Kreiss
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Lucki
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D017660:Autoreceptors / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*
D017660:Autoreceptors; D011985:Receptors, Serotonin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011433:Propranolol