Effects of 5-HT and 8-OH-DPAT on forebrain monoamine synthesis after local application into the median and dorsal raphe nuclei of the rat.
5-HT (10 and 40 micrograms) and 8-OH-DPAT (1 and 5 micrograms) were locally applied into the dorsal or median raphe nuclei in awake, unrestrained, rats. All animals were also treated with the 5-HTP and DOPA decarboxylase inhibitor NSD-1015, 100 mg kg-1 SC, 30 min before decapitation. 5-HT or 8-OH-DPAT were administered 5 min before NSD-1015. The regional brain in vivo rate of tyrosine and tryptophan hydroxylase activity was estimated by measuring the accumulation of DOPA and 5-HTP. The following brain regions were sampled: neocortex, hippocampus, dorso-lateral neostriatum, ventro-medial neostriatum, nucleus accumbens, olfactory tubercle, globus pallidus, septum and the amygdala. Compared to normal controls, there were small and inconsistent effects on forebrain 5-HTP accumulation by saline injections into the dorsal or the median raphe (an increase in 3 out of 36 experiments), whereas strong effects by the injection procedure were noted on forebrain DOPA accumulation (an increase in 15 out of 36 experiments). Injections of 5-HT (same effect by 10 or 40 micrograms) into the dorsal raphe, produced a decrease in 5-HTP accumulation in all forebrain areas except for the hippocampus and the septum, whereas no effects were seen in any area after median raphe injections. In contrast, 8-OH-DPAT preferentially produced a decrease in forebrain 5-HTP accumulation after median raphe injections and less, but statistically significant effects by dorsal raphe injections. The 8-OH-DPAT injection into the median raphe primarily affected limbic forebrain areas (hippocampus, nucleus accumbens, ventro-medial neostriatum, amygdala and the septum). This dissociation of the effects of 5-HT and 8-OH-DPAT on forebrain 5-HT synthesis after local application into the dorsal or the median raphe strongly supports the contention of heterogeniety in the brain 5-HT receptor population in terms of receptor subtypes and/or receptor regulation.
Hillegaart
V
V
Department of Psychology, University of Göteborg, Sweden.
Hjorth
S
S
Ahlenius
S
S
D006916:5-Hydroxytryptophan / Q000378:metabolism*; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D002395:Catecholamines; D004791:Enzyme Inhibitors; D006834:Hydrazines; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D004295:Dihydroxyphenylalanine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan