Abstract
Rationale
Dopamine D3 receptor-preferring ligands may be able to modify the conditioned reinforcing effects of drug-associated stimuli. In evaluating the effects of these compounds, it is important to clarify the extent to which responding depends on (1) conditioned reinforcement vs. other behavioral mechanisms and (2) dopamine D3 vs. D2 receptor activity.
Objectives
To use behaviorally stringent new-response acquisition procedures to characterize the effects of the D3-preferring agonist, pramipexole, on the conditioned reinforcing effects of a stimulus paired with the opioid agonist, remifentanil.
Methods
First, in Pavlovian conditioning (PAV) sessions, rats received response-independent IV injections of remifentanil and presentations of a light–noise stimulus. In separate groups, injections and stimuli either always co-occurred (“paired PAV”) or occurred with no consistent relationship (“random PAV” control). Next, in instrumental acquisition (ACQ) sessions, all animals could respond in two nose-poke manipulanda: an active nose-poke, which produced the stimulus alone, or an inactive nose-poke. Pramipexole was injected SC prior to ACQ sessions with or without pretreatments of the D3-preferring antagonist, SB-277011A, or the D2-preferring antagonist, L-741,626.
Results
After paired PAV, but not random PAV, rats acquired nose-poke responding during ACQ (i.e., active > inactive). Pramipexole dose-dependently increased active responding without changing inactive responding. Pramipexole-induced increases in responding were blocked by pretreatment with L-741,626, but not SB-277011A.
Conclusions
Pramipexole specifically enhanced remifentanil-conditioned reinforcement: active responding was selectively increased only after the stimulus was paired with remifentanil. Although pramipexole is D3-preferring, the antagonist effects obtained presently suggest an important role for the D2 receptor in opioid-conditioned reinforcement.
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Acknowledgments
We thank Davina Barron, Alyssa Cunningham, and Tomas Davaloz for their excellent technical assistance. We thank Gail Winger for her comments on an earlier draft of the manuscript. This research was supported by the National Institute on Drug Abuse under grants T32DA07268, R01DA020669, R01DA024897, and R01DA032943 and by the National Science Foundation Graduate Research Fellowship Program under grant DGE 0718128.
Conflict of interest
The authors declare no conflicts of interest. All experiments comply with the current laws of the United States, the country in which they were performed.
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Bertz, J.W., Chen, J. & Woods, J.H. Effects of pramipexole on the acquisition of responding with opioid-conditioned reinforcement in the rat. Psychopharmacology 232, 209–221 (2015). https://doi.org/10.1007/s00213-014-3659-2
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DOI: https://doi.org/10.1007/s00213-014-3659-2