Evidence for selective inhibition of limbic forebrain dopamine synthesis by 8-OH-DPAT in the rat

Summary Regional dopamine synthesis in the rat striatum was estimated by measuring DOPA accumulation following inhibition of cerebral aromatic l-amino acid decarboxylase by means of NSD-1015, 100 mg kg^–1 intraperitoneally. In animals treated with reserpine, 5 mg kg^–1 subcutaneously –18 h, there was a statistically significant increase in DOPA accumulation in the nucleus accumbens, the ventro-medial neostriatum, the dorso-lateral neostriatum and in the posterior limb of the neostriatum. This increase in DOPA accumulation was antagonized dose-dependently in the nucleus accumbens and ventro-medial neostriatum, but not in the other two regions, by treatment with the 5-HT_1A receptor agonist 8-OH-DPAT, 0.15–2.4 mol kg^–1, whereas the partial dopamine D₂ receptor agonist (–)3-PPP, 2.5–10.0 mol kg^–1, or the full dopamine D₂ receptor agonist quinpirole, 0.05–0.8 mol kg^–, antagonized the reserpine-induced increase in DOPA accumulation uniformly in all four regions of the striatum. The suppression of DOPA accumulation by 8-OH-DPAT in reserpine-treated animals, was completely antagonized by raclopride, 1 mol kg^–1, but not by (–)pindolol, 8 mol kg^–1. The accumulation of 5-HTP in all regions of the striatum as well as in the neocortex following decarboxylase inhibition and reserpine pretreatment, was also inhibited by 8-OH-DPAT, and this inhibition was unaffected by treatment with raclopride or (–)pindolol. It is concluded that 8-OH-DPAT, in addition to general effects on forebrain 5-hydroxytryptamine synthesis, selectively affects limbic forebrain dopamine synthesis. This latter effect is probably due to direct stimulation of dopamine autoreceptors, since it was obtained in reserpine-treated rats, and was completely antagonized by raclopride, but not (–)pindolol.Presented in part at the 7th General Meeting of the European Society for Neurochemistry, June 12–17th 1988, Göteborg, SwedenSend offprint requests to S. Ahlenius at the above address