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.

The control of ingestive behavior by the median raphe nucleus

“…These findings suggest that the feeding induced by these manipulations may be mediated through accumbens dopamine release, a possibility supported by the fact that injections of dopamine agonists directly into the accumbens are able to stimulate food intake (Swanson et al, 1997). In this context, it is striking that accumbens dopamine metabolism is also increased following intra-MR injections of a number of compounds which stimulate ingestive behavior including muscimol, the GABA B agonist baclofen and the EAA antagonist 2-amino,5-phosphonovaleric acid (Wirtshafter & Trifunovic, 1992;Wirtshafter et al, , 1993, but not 8-OH-DPAT (Hillegaart et al, 1990). (It should be noted that nothing is known about the pathways or mechanisms through which inactivation of the MR alters dopamine turnover.)…”

Facilitation and inhibition of male rat ejaculatory behaviour by the respective 5‐HT1Aand 5‐HT1Breceptor agonists 8‐OH‐DPAT and anpirtoline, as evidenced by use of the corresponding new and selective receptor antagonists NAD‐299 and NAS‐181

“…Thus, for example, (7)-pindolol can antagonize the 8-OH-DPATinduced facilitation of male rat ejaculatory behaviour (Ahlenius & Larsson, 1988). In addition, (7)-pindolol treatment will enhance the 5-HTP-induced inhibition of male rat ejaculatory behaviour (Ahlenius & Larsson, 1991a;, presumably due to disinhibition of autoreceptor-mediated inhibition of ®ring in serotonergic neurons (see Aghajanian, 1995), as well as in synthesis (Hjorth et al, 1982;Hillegaart et al, 1990) and release (Hutson et al, 1989;Sharp et al, 1989) of forebrain serotonin. In support for this view, the inhibition of male rat ejaculatory behaviour produced by 5-HTP was also enhanced by pretreatment with the 5-HT 1A receptor antagonist WAY-100635 (Ahlenius & Larsson, 1998).…”

Potency mismatch for behavioral and biochemical effects by dopamine receptor antagonists: implications for the mechanism of action of clozapine

“…The mean weight ± SD (rag) of these brain areas (n = 40) were as follows: 13.5 ± 2.0 (prefrontal cortex), 24.3 ± 1.9 (dorso-lateral neostriatum), 34.8 ± 3.2 (ventral neostriatum), 27.1 ± 4.3 ( posterior neostriatum). For further details on the dissection procedures see Hillegaart et al (1990). The brain samples were immediately frozen on dry ice and stored at -70°C until processing.…”