The reinforcing properties of salsolinol in the ventral tegmental area: Evidence for regional heterogeneity and the involvement of serotonin and dopamine

Background: Salsolinol (SAL), the condensation product of acetaldehyde and dopamine, may be a factor contributing to alcohol abuse. Previous research indicated that both ethanol and acetaldehyde are self-administered into the posterior ventral tegmental area (VTA). The current study examined SAL self-infusions into the VTA, and determined the involvement of dopamine neurons and 5-HT3 receptors in this process. Methods: The intracranial self-administration technique was used to determine the self-infusion of SAL into the VTA of adult, male Wistar rats. The rats were placed in 2-lever (active and inactive) experimental chambers, and allowed to respond for the self-infusion of 0, 0.03, 0.1, 0.3, 1.0 or 3.0 mu M SAL into the posterior or anterior VTA. In a second experiment, rats self-administered 0.3 mu M SAL for the initial 4 sessions, co-administered SAL with ICS-205,930 (a 5-HT3 receptor antagonist) or quinpirole (a D-2,D-3 receptor agonist) for sessions 5 and 6, and then only 0.3 mu M SAL for session 7. Results: Wistar rats, given 0.03 to 0.3 mu M SAL, received more infusions per session than did the group given artificial cerebrospinal fluid (aCSF) alone (e.g., 41 infusions for 0.1 mu M SAL versus 9 infusions for the aCSF group), and responded more on the active than inactive lever. These effects were observed in the posterior but not in anterior VTA. Co-infusion of 100 mu M ICS-205,930, or quinpirole significantly reduced self-infusions and active lever responding. Conclusions: SAL produces reinforcing effects in the posterior VTA of Wistar rats, and these effects are mediated by activation of DA neurons and local 5-HT3 receptors.