It has recently been demonstrated that the ventral pallidum receives a direct """"""""mesopallidal"""""""" dopamine projection from the ventral tegmental area. Accumulating data suggests that this mesopallidal dopamine system play a very important role in psychostimulant-induced locomotor activation and reward. The major objective of this proposal is to characterize this mesopallidal dopamine activity in the action of psychostimulants. In vivo microdialysis will be performed in order to monitor changes in extracellular dopamine at the ventral pallidum in response to cocaine injections and during cocaine self-administration. As a comparison, the cocaine-induced increase in extracellular dopamine at the nucleus accumbens will also be monitored. The results of these studies are critical for our understanding the neurobiological mechanism of cocaine abuse, and may have important implications in the treatment of cocaine addiction. In addition, it will add to general knowledge of the mesolimbic system, a system which has a well established role in the vulnerability to drug addiction and psychiatric disorders.
| Goodwin, Amy K; Mueller, Melanie; Shell, Courtney D et al. (2013) Behavioral effects and pharmacokinetics of (±)-3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) after intragastric administration to baboons. J Pharmacol Exp Ther 345:342-53 |
| Mueller, Melanie; Yuan, Jie; Maldonado Adrian, Concepcion et al. (2011) Inhibition of 3,4-methylenedioxymethamphetamine metabolism leads to marked decrease in 3,4-dihydroxymethamphetamine formation but no change in serotonin neurotoxicity: implications for mechanisms of neurotoxicity. Synapse 65:983-90 |
| Mueller, Melanie; Goodwin, Amy K; Ator, Nancy A et al. (2011) Metabolism and disposition of 3,4-methylenedioxymethamphetamine (""ecstasy"") in baboons after oral administration: comparison with humans reveals marked differences. J Pharmacol Exp Ther 338:310-7 |
