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Updated: Mar 15, 2026

Reinstatement of Drug-seeking in Mice Using the Conditioned Place Preference Paradigm
Published on: June 7, 2018
Dopamine D1 and D3 receptor interactions in cocaine reward and seeking in rats
E Galaj1, W Harding2,3,4, R Ranaldi5,6,7
1Neuropsychology Doctoral Program, The Graduate Center of the City University of New York, New York, NY, 10016, USA.
Rationale:
Animal research has demonstrated a role of dopamine D1 and D3 receptors in cocaine reward and seeking.
Purpose And Methods:
Here, we investigated the potential interaction of these two dopamine receptors in cue-induced reinstatement of cocaine seeking, cocaine conditioned place preference (CPP), and cocaine self-administration in rats.
Results:
The co-administration of a D3 receptor antagonist, NGB 2904 and a D1 partial agonist, SKF 77434, of doses which when administered individually produced no significant effects, prior to reinstatement or CPP tests significantly reduced lever pressing and time spent in the cocaine-paired environment, suggesting synergistic effects of the combined compounds on cocaine seeking. When given to rats self-administering cocaine under a progressive ratio schedule of reinforcement doses of NGB 2904 which were ineffective alone significantly enhanced the break point-reducing effects of SKF 77434.
Conclusions:
Our results indicate that the combined treatment with a D1 receptor partial agonist and D3 receptor antagonist produces robust decreases in cocaine seeking and reward. This suggests an interaction between dopamine D1 and D3 receptors in cocaine-related behaviors.
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