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Medial prefrontal cannabinoid CB1 receptors modulate consolidation and extinction of cocaine-associated memory in mice

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Abstract

Rationale

Cannabinoid CB1 receptors are implicated in various forms of learning and memory, including acquisition and reinstatement of cocaine-associated memory. However, roles of CB1 receptors in consolidation and extinction processes of cocaine-associated memory and the brain areas potentially involved remain unknown.

Objective

This study examined the effect of rimonabant, a CB1 receptor antagonist, administered systemically or directly into the medial prefrontal cortex (mPFC) on memory consolidation and extinction of cocaine-induced conditioned place preference (CPP).

Materials and methods

Male C57BL/6J mice were trained to acquire cocaine-induced CPP. Rimonabant (0.1–3 mg/kg, i.p. or 1.5 μg bilaterally in the mPFC) or vehicle was administered either immediately after each CPP training (consolidation) or forced extinction (extinction) trial. Cocaine-induced CPP was tested after training, extinction, or cocaine priming.

Results

Systemic or intra-mPFC administration of rimonabant impaired consolidation of CPP induced by a high dose (20 or 40 mg/kg) of cocaine but facilitated that induced by a low dose (2.5, 5, or 10 mg/kg). Moreover, systemic or intra-mPFC administration of rimonabant enhanced extinction of CPP memory induced by a high-dose (20 mg/kg) cocaine.

Conclusion

Our results suggest that antagonism of CB1 receptors in the mPFC bidirectionally modulates consolidation but facilitates extinction of cocaine-induced CPP memory. Therefore, CB1 receptor blockade with the concomitant extinction behavioral procedure may hint important therapeutic intervention strategies for the heavy cocaine addicts in a clinical setting.

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Acknowledgments

We thank Drs. Keng-Chen Liang and Tsu-Wei Wang for comments and suggestions on the manuscript; Heng-Ai Chang for help with the experiment; Li-Hsien Chen and Wen-Yu Tzeng for technical assistance; and all the members of the Hu lab for their support. This work was supported by ROC National Science Council grant Nos. 100-2410-H-006-085-MY2, 101-2320-B-006-007-, and 102-2410-H-006-016-MY2 to S.S.H.; No. 101-2922-I-006-338 to L.Y.; and by NCKU Aiming for the Top University and Elite Research Center Development Plan (MoE ATU Plan) to S.S.H.. The authors declare no financial conflict of interest.

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Authors and Affiliations

  1. Cannabinoid Signaling Laboratory, Department of Psychology, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan

    Sherry Shu-Jung Hu

  2. Institute of Cognitive Science, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan

    Sherry Shu-Jung Hu & Ya-Wei Liu

  3. Behavioral Neuropharmacology Laboratory, Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan

    Lung Yu

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  1. Sherry Shu-Jung Hu
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  2. Ya-Wei Liu
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  3. Lung Yu
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Correspondence to Sherry Shu-Jung Hu or Lung Yu.

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Hu, S.SJ., Liu, YW. & Yu, L. Medial prefrontal cannabinoid CB1 receptors modulate consolidation and extinction of cocaine-associated memory in mice. Psychopharmacology 232, 1803–1815 (2015). https://doi.org/10.1007/s00213-014-3812-y

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