A role for nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior
Section snippets
Subjects
All experiments were conducted according to specifications of the National Institute of Health guide for the Care and Use of Laboratory Animals. Male Sprague–Dawley rats (Simmonsen, Gilroy, CA) weighing 300–350 g at the beginning of the experiment were housed under a 12 h light-dark cycle and had ad libitum access to food and water, except where food restrictions applied as outlined below. Animals were individually housed after surgery and all experiments were performed during the light cycle.
Drugs
Results
Figure 1 shows the effect of glutamate receptor agonist or antagonist administration into the nucleus accumbens on the maintenance of cocaine self-administration. All groups analysed showed significant discrimination between the infusion and inactive levers (P<0.003). Neither saline nor DMSO (20%) treatment significantly altered infusion lever responses and the data have been pooled (Fig. 1A, B). Figure 1A and B shows that pretreatment with either AMPA (0.4 nmol/side) or cis-ACDA (3 nmol/side)
Discussion
The present results describe a role for AMPA or NMDA receptor activation in the nucleus accumbens in maintaining cocaine self-administration or for initiating the relapse to cocaine-seeking behavior. AMPA or NMDA receptor stimulation in the nucleus accumbens during the maintenance of cocaine self-administration caused a significant leftward shift of the cocaine dose–response curve to suggest an enhancement of cocaine reward. In addition, the intra-accumbens administration of AMPA or NMDA
Conclusions
This study demonstrates a facilitatory effect of increased glutamate transmission in the nucleus accumbens on the rewarding efficacy of cocaine and on the reinstatement of cocaine-seeking behavior. These results imply that changes in glutamate transmission detected in rats sensitized to non-contingent cocaine administration at least in part parallel those alterations which are observed in animals withdrawn from contingent cocaine-taking. Therefore, changes in nucleus accumbens glutamate
Acknowledgements
We thank Jenny Baylon for her assistance in the preparation of this manuscript and Anastasia J. Romanides and Mathew Edwards for their technical assistance. This research was supported in part by the Washington State Alcohol and Drug Abuse Program and USPHS grants MH-40817 and DA-03906, and a Research Career Development Award DA-00158 (PWK).
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