Increased dopamine turnover in the ventral striatum by 8-OH-DPAT administration in the rat

Abstract

The administration of the 5-HT_1A agonist 8-OH-DPAT (0.8 μmol kg⁻¹ s.c. — 40 min) produced an increase in dopamine (DA) turnover, estimated by the quotient (DOPAC + HVA) DA⁻¹, in the ventral striatum of the rat. No statistically significant effects were obtained in the dorsal striatum. The accumulation of 3-MT in pargyline-treated animals (375 μmol kg⁻¹ s.c.— 60 min) was not affected by 8-OH-DPAT treatment (0.15-2.4 μmol kg⁻¹ s.c.-30 min). These findings indicate that 8-OH-DPAT has weak antagonist properties at striatal DA receptors in normal rats. Both the 5-HT_1A agonist flesinoxan (0.06–17.8 μmol kg⁻¹ s.c. — 50 min) and the mixed 5-HT₁ and 5-HT₂ agonist 5-MeODMT (1.6–26.0 μmol kg⁻¹ s.c. −50 min) produced a decrease in forebrain 5-HTP accumulation (striatum and neocortex), following decarboxylase inhibition by means of NSD-1015 in reserpine treated rats, indicating stimulation of central 5-HT receptors by these two compounds. At the same time, the DOPA accumulation in the ventral striatum was decreased by flesinoxan and increased by 5-MeODMT treatment. These observations show that, under these conditions, the decrease in DA synthesis is not directly coupled to the decreased 5-HT synthesis produced by flesinoxan, as previously demonstrated for 8-OH-DPAT. Taken together with previous observations, the present results suggest that 8-OH-DPAT, depending on the experimental conditions, is an agonist or antagonist at striatal DA receptors, in all probability due to partial DA receptor agonist properties of the compound.