Activation of 5-HT(1B/1D) receptors in the mesolimbic dopamine system increases dopamine release from the nucleus...

This study was designed to investigate the role of 5-hydroxytryptamine (5-HT)(1B) receptors located in the ventral tegmental area and nucleus accumbens in the modulation of accumbal dopaminergic transmission. The selective 5-HT(1B) receptor agonist CP 93129 [3-(1,2,5,6-tetrahydro-4-pyridyl)pyrrolo[3,2-b]pyrid-5-one] was administered into the ventral tegmental area or nucleus accumbens of freely moving Sprague-Dawley rats via retrograde microdialysis. The effects of intra-accumbal and intra-tegmental CP 93129 on extracellular dopamine levels in the nucleus accumbens were measured using one- and dual-probe microdialysis, respectively. For dual-probe microdialysis, one probe was in the ventral tegmental area for drug administration and the other in the ipsilateral nucleus accumbens for dopamine measurement. The results show that infusion of CP 93129 (2, 5 and 10 microM) into the nucleus accumbens increased local dopamine levels in a concentration-related manner. Infusion of CP 93129 (10 and 20 microM) into the ventral tegmental area also increased dopamine levels in the ipsilateral nucleus accumbens. The increased dopamine release in the nucleus accumbens produced by intra-accumbal or intra-tegmental CP 93129 was antagonized by co-infusion of cyanopindolol (5 microM), a 5-HT(1B/1A) receptor antagonist, but not by WAY-100635 [N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinyl-cyclohexanecarboxamide] (5 microM), a highly selective 5-HT(1A) receptor antagonist. In addition, augmentations of dopamine release in the nucleus accumbens induced by intra-accumbal CP 93129 were sensitive to Na(+) channel blockade with tetrodotoxin. These results are not in opposition to the concept that 5-HT(1B) receptors within the ventral tegmental area and nucleus accumbens are all involved in the modulation of dopamine release in the terminal area of the mesolimbic dopamine system.