Affiliation:
1. Departments of Neuropharmacology and Bioanalysis, S-151 85 Södertälje, Sweden
2. Astra Research Centre AB, S-151 85 Södertälje, Sweden
Abstract
Abstract
The administration of the 5-HT1A 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-HT1A 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.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
30 articles.
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