Memantine Prevents the WIN 55,212-2 Evoked Cross-Priming of Ethanol-Induced Conditioned Place Preference (CPP)

International Journal of Molecular Sciences

Paulina Surowka¹  Malgorzata Filip²  Irena Smaga²  Marta Marszalek-Grabska³  Jolanta H. Kotlinska⁴  Pawel Grochecki⁴  Tymoteusz Slowik⁵ 

[1] Affective Cognitive Neuroscience Laboratory, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Poland;Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Poland;Department of Experimental and Clinical Pharmacology, Medical University of Lublin, 20-090 Lublin, Poland;Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland;Experimental Medicine Center, Medical University of Lublin, 20-090 Lublin, Poland;

关键词: cannabinoid;    glutamate;    CNR1;    GRIN1;    GRIN2A;    ethanol relapse;   

DOI  :  10.3390/ijms22157940

来源: DOAJ

【 摘 要 】

The activation of the endocannabinoid system controls the release of many neurotransmitters involved in the brain reward pathways, including glutamate. Both endocannabinoid and glutamate systems are crucial for alcohol relapse. In the present study, we hypothesize that N-methyl-D-aspartate (NMDA) glutamate receptors regulate the ability of a priming dose of WIN 55,212-2 to cross-reinstate ethanol-induced conditioned place preference (CPP). To test this hypothesis, ethanol-induced (1.0 g/kg, 10% w/v, i.p.) CPP (unbiased method) was established using male adult Wistar rats. After CPP extinction, one group of animals received WIN 55,212-2 (1.0 and 2.0 mg/kg, i.p.), the cannabinoid receptor 1 (CB1) agonist, or ethanol, and the other group received memantine (3.0 or 10 mg/kg, i.p.), the NMDA antagonist and WIN 55,212-2 on the reinstatement day. Our results showed that a priming injection of WIN 55,212-2 (2.0 mg/kg, i.p.) reinstated (cross-reinstated) ethanol-induced CPP with similar efficacy to ethanol. Memantine (3.0 or 10 mg/kg, i.p.) pretreatment blocked this WIN 55,212-2 effect. Furthermore, our experiments indicated that ethanol withdrawal (7 days withdrawal after 10 days ethanol administration) down-regulated the CNR1 (encoding CB1), GRIN1/2A (encoding GluN1 and GluN2A subunit of the NMDA receptor) genes expression in the prefrontal cortex and dorsal striatum, but up-regulated these in the hippocampus, confirming the involvement of these receptors in ethanol rewarding effects. Thus, our results show that the endocannabinoid system is involved in the motivational properties of ethanol, and glutamate may control cannabinoid induced relapse into ethanol seeking behavior.

【 授权许可】

Unknown