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 microM SAL into the posterior or anterior VTA. In a second experiment, rats self-administered 0.3 microM 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 microM SAL for session 7.


RESULTS
Wistar rats, given 0.03 to 0.3 microM SAL, received more infusions per session than did the group given artificial cerebrospinal fluid (aCSF) alone (e.g., 41 infusions for 0.1 microM 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 microM 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.
Rodd
Zachary A
ZA
Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana 46202-4887, USA. zrodd@iupui.edu
Oster
Scott M
SM
Ding
Zheng-Ming
ZM
Toalston
Jamie E
JE
Deehan
Gerald
G
Bell
Richard L
RL
Li
Ting-Kai
TK
McBride
William J
WJ
D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001931:Brain Mapping; D004298:Dopamine / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D050637:Receptors, Dopamine D3 / Q000187:drug effects / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000502:physiology; D012646:Self Administration; D012701:Serotonin / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000503:physiopathology
D007546:Isoquinolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; C036617:salsolinol; D004298:Dopamine