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.

Abstract

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.

• Authors: V Hillegaart, S Hjorth, S Ahlenius
• Journal: Journal of neural transmission. General section (J Neural Transm Gen Sect) Vol. 81 Issue 2 Pg. 131-45 ( 1990) Austria
• PMID: 2141990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catecholamines
• Enzyme Inhibitors
• Hydrazines
• Naphthalenes
• Tetrahydronaphthalenes
• Serotonin
• Dihydroxyphenylalanine
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• 3-hydroxybenzylhydrazine
• 5-Hydroxytryptophan

Topics

• 5-Hydroxytryptophan (metabolism)
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Animals
• Catecholamines (metabolism)
• Dihydroxyphenylalanine (metabolism)
• Enzyme Inhibitors (pharmacology)
• Frontal Lobe (drug effects, metabolism)
• Hydrazines (pharmacology)
• Male
• Naphthalenes (pharmacology)
• Raphe Nuclei (drug effects, metabolism)
• Rats
• Rats, Inbred Strains
• Serotonin (pharmacology)
• Tetrahydronaphthalenes (pharmacology)