Reserpine modulates serotonin transporter mRNA levels in the rat brain

Despite recent advances in determining central serotonin (5-HT) function, t he basic aspects by which serotonin neurotransmission is controlled and reg ulated are still not understood. Since the serotonin transporter (5-HTT) is involved in terminating the action of 5-HT that is released from the presy naptic nerve terminal, the regulation of 5-HTT may be an important step in controlling 5-HT neurotransmission at the synaptic cleft. The present study investigated the effects of reserpine administration on 5-HTT gene express ion as well as on tryptophan hydroxylase (TPH) expression in the rat brain. Male Sprague-Dawley rats were injected with reserpine (10 mg/kg, i.p.) and sacrificed at 8 h, 3 days, 7 days or 21 days after the injection. Control rats were injected with saline and sacrificed either at 8 h or 21 days afte r the injection. The midbrain region was dissected, RNA was isolated and pr obed fbr 5-HTT expression using Northern Blotting. Data were analyzed using Super-Anova followed by post-hoc Dunnett's test. While mRNA levels for 5-H TT were unchanged at 8 h after reserpine, a significant decrease was noted at 3 days and 7 days (F=10; p<0.0001). 5-HTT mRNA levels returned to contro l levels by 21 days. In contrast, TPH expression was unaltered at all time points examined. The results of this study provide useful information regar ding the role that the 5-HTT may be playing in the homeostatic control of 5 -HT neurotransmission at the synapse.