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 μM SAL into the posterior or anterior VTA. In a second experiment, rats self-administered 0.3 μM SAL for the initial 4 sessions, co-administered SAL with ICS-205,930 (a 5-HT₃ receptor antagonist) or quinpirole (a D_2,3 receptor agonist) for sessions 5 and 6, and then only 0.3 μM SAL for session 7.
Results:  Wistar rats, given 0.03 to 0.3 μM SAL, received more infusions per session than did the group given artificial cerebrospinal fluid (aCSF) alone (e.g., 41 infusions for 0.1 μM 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 μM 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.