The 5-HT 1A receptor agonist, 8-OH-DPAT, preferentially activates cell body 5-HT autoreceptors in rat brain in vivo.
The present study was undertaken in an attempt to assess whether the effects of the potent and selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, on cerebral 5-hydroxytryptamine (5-HT) neurochemistry in vivo are mediated via 5-HT autoreceptors on the cell bodies or on the terminals, and or via postsynaptic 5-HT receptors. To this end we determined in vivo indices of 5-HT synthesis and release/turnover rates in a number of prominent 5-HT neuronal projection areas in the CNS i) after systemic administration of 8-OH-DPAT to rats with an acute unilateral axotomy of the ascending mesencephalic monoamine neurones, or ii) after local infusion of the compound into the dorsal raphé (DRN) 5-HT cell body region of intact rats. Transection did not alter 5-HT synthesis per se, but prevented the synthesis-inhibitory effect of 8-OH-DPAT. Thus, the 5-HT synthesis-inhibiting action of 8-OH-DPAT is highly dependent upon intact impulse flow in the central 5-HT neurones. On the other hand, local DRN application of the compound (1 microgram) resulted in a clearcut reduction of the 5-HT synthesis and release indices measured in 5-HT terminals in, e.g., the striatum. These findings provide direct neurochemical evidence that by preferentially stimulating somatodendritic 5-HT1A receptors, 8-OH-DPAT inhibits the 5-HT neuronal impulse flow, thereby effectuating decreased terminal 5-HT synthesis and release.(ABSTRACT TRUNCATED AT 250 WORDS)
Hjorth
S
S
Department of Pharmacology, University of Göteborg, Sweden.
Magnusson
T
T
D006916:5-Hydroxytryptophan / Q000032:analysis; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000601:surgery; D001923:Brain Chemistry; D004295:Dihydroxyphenylalanine / Q000032:analysis; D004298:Dopamine / Q000032:analysis / Q000096:biosynthesis; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000032:analysis / Q000096:biosynthesis; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004295:Dihydroxyphenylalanine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan; D004298:Dopamine