Received for publication August 19, 2004.
Revised December 1, 2004.
Accepted for publication December 1, 2004.

Intracranial Self-Administration of Cocaine within the Posterior Ventral Tegmental Area of Wistar Rats: Evidence for Involvement of Serotonin-3 Receptors and Dopamine Neurons

Abstract

The rewarding properties of cocaine have been postulated to be regulated, in part, by the mesolimbic dopamine (DA) system. The present study assessed whether adult female Wistar rats would self-administer cocaine directly into the VTA. Following guide cannulae surgery aimed at either the posterior or anterior VTA, subjects were placed in an operant box equipped with an 'active lever' that caused the delivery of the infusate and an 'inactive lever' that did not. Posterior and anterior VTA subjects were randomly assigned to one of six groups that self-administered either artificial CSF (aCSF) or 25 to 400 pmol cocaine/100 nl in aCSF for the first four sessions, aCSF in sessions 5 and 6, and the acquisition dose of infusate during session 7. Additionally, the effects of increasing the 'time-out' period, higher concentrations of cocaine, co-administration of a 5HT3 antagonist, and co-administration of a D2/3 agonist on self-infusion of cocaine were determined. Self-infusions were maintained when the 'time-out' period was extended from 5 to 25 sec. Co-infusion of a 5HT3 antagonist or D2/3 agonist blocked the self-infusion of cocaine. In contrast, rats did not self-administer 25-400 pmol/100 nl cocaine into the anterior VTA. Additionally, rats did not self-administer either 800 or 1600 pmol/100 nl cocaine into the posterior or anterior VTA. Overall, the data indicate that the VTA is functionally heterogeneous with regard to the rewarding actions of cocaine, and that the reinforcing effects of cocaine within the posterior VTA are mediated by activation 5-HT3 receptors and DA neurons.

Key words: Intracranial Self-Administration, Ventral Tegmental Area, cocaine, dopamine, reinforcement, serotonin

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