Effects of serotonin depletion by p-chlorophenylalanine, p-chloroamphetamine or 5,7-dihydroxytryptamine on central dopaminergic neurons: Focus on tuberoinfundibular dopaminergic neurons and serum prolactin

Three serotonin (5-HT) neurotoxins, p-chlorophenylalanine (PCPA, 125 and 25 0 mg/kg, i.p.), p-chloroamphetamine (PCA, 10 mg/kg, i.p.) and 5,7-dihydroxy tryptamine (5,7-DHT, 200 mu g/rat, i.c.v.) were used to examine whether dep letion of central 5-HT has an effect on central dopaminergic (DA) neuronal activities or on prolactin (PRL) secretion. Adult ovariectomized Sprague-Da wley rats primed with estrogen (polyestradiol phosphate, 0.1 mg/ rat, s.c.) were treated with one of three neurotoxins and then decapitated in the mor ning after 3-7 days. Blood sample a nd brain tissues we re collected. The a cute effect of PCA (from 30 to 180 min) was also determined. The concentrat ions of 5-HT, DA and their metabolites, 5-hydroxyindoleacetic acid and 3,4- dihydroxyphenylacetic acid, in the median eminence, striatum and nucleus ac cumbens were determined by HPLC-electrochemical detection. All three toxins significantly depleted central 5-HT stores by 11-20%. Except for PCPA, nei ther PCA nor 5,7-DHT had any significant effect on basal DA neuronal activi ties or PRL secretion. PCA also exhibited an acute effect on the release an d reuptake of 5-HT and DA. In summary, depletion of central 5-HT stores to a significant extent for 3-7 days did not seem to affect basal DA neuronal activity and PRL secretion.