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

Abstract

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-HT1A receptor agonist 8-OH-DPAT, 0.15-2.4 mumol kg-1, whereas the partial dopamine D2 receptor agonist (-)3-PPP, 2.5-10.0 mumol kg-1, or the full dopamine D2 receptor agonist quinpirole, 0.05-0.8 mumol kg-1, 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 mumol kg-1, but not by (-)pindolol, 8 mumol 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.(ABSTRACT TRUNCATED AT 250 WORDS)