Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress |
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Authors: | Rocío Guerrero-Bautista Aurelio Franco-García Juana M Hidalgo Francisco Jos Fernndez-Gmez Bruno Ribeiro Do Couto M Victoria Milans Cristina Núez |
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Affiliation: | 1.Group of Cellular and Molecular Pharmacology, Department of Pharmacology, University of Murcia, 30120 Murcia, Spain; (R.G.-B.); (A.F.-G.); (J.M.H.); (F.J.F.-G.);2.Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 Murcia, Spain;3.Department of Anatomy and Psychobiology, University of Murcia, 30100 Murcia, Spain |
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Abstract: | Relapse in the seeking and intake of cocaine is one of the main challenges when treating its addiction. Among the triggering factors for the recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which are responsible for emotional and episodic memories. Moreover, D3 receptor (D3R) antagonists have recently arisen as a potential treatment for preventing drug relapse. Thus, we have assessed the impact of D3R blockade in the expression of some dopaminergic markers and the activity of the mTOR pathway, which is modulated by D3R, in the BLA and DG during the reinstatement of cocaine-induced conditioned place preference (CPP) evoked by drug priming and social stress. Reinstatement of cocaine CPP paralleled an increasing trend in D3R and dopamine transporter (DAT) levels in the BLA. Social stress, but not drug-induced reactivation of cocaine memories, was prevented by systemic administration of SB-277011-A (a selective D3R antagonist), which was able, however, to impede D3R and DAT up-regulation in the BLA during CPP reinstatement evoked by both stress and cocaine. Concomitant with cocaine CPP reactivation, a diminution in mTOR phosphorylation (activation) in the BLA and DG occurred, which was inhibited by D3R blockade in both nuclei before the social stress episode and only in the BLA when CPP reinstatement was provoked by a cocaine prime. Our data, while supporting a main role for D3R signalling in the BLA in the reactivation of cocaine memories evoked by social stress, indicate that different neural circuits and signalling mechanisms might mediate in the reinstatement of cocaine-seeking behaviours depending upon the triggering stimuli. |
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Keywords: | cocaine conditioned place preference reinstatement dopamine D3 receptor social stress |
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