Cannabidiol Protects against the Reinstatement of Oxycodone-Induced Conditioned Place Preference in Adolescent Male but Not Female Rats: The Role of MOR and CB1R

Author:

Socha Justyna1,Grochecki Pawel1ORCID,Marszalek-Grabska Marta2ORCID,Skrok Aleksandra1,Smaga Irena3ORCID,Slowik Tymoteusz4,Prazmo Wojciech5,Kotlinski Robert6,Filip Malgorzata3ORCID,Kotlinska Jolanta H.1ORCID

Affiliation:

1. Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland

2. Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8b, 20-090 Lublin, Poland

3. Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland

4. Experimental Medicine Center, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland

5. Breast Surgery Department, Provincial Specialist Hospital, Al. Krasnicka 100, 20-718 Lublin, Poland

6. Clinical Department of Cardiac Surgery, University of Rzeszow, Lwowska 60, 35-301 Rzeszow, Poland

Abstract

Cannabidiol (CBD), a phytocannabinoid, appeared to satisfy several criteria for a safe approach to preventing drug-taking behavior, including opioids. However, most successful preclinical and clinical results come from studies in adult males. We examined whether systemic injections of CBD (10 mg/kg, i.p.) during extinction of oxycodone (OXY, 3 mg/kg, i.p.) induced conditioned place preference (CPP) could attenuate the reinstatement of CPP brought about by OXY (1.5 mg/kg, i.p.) priming in adolescent rats of both sexes, and whether this effect is sex dependent. Accordingly, a priming dose of OXY produced reinstatement of the previously extinguished CPP in males and females. In both sexes, this effect was linked to locomotor sensitization that was blunted by CBD pretreatments. However, CBD was able to prevent the reinstatement of OXY-induced CPP only in adolescent males and this outcome was associated with an increased cannabinoid 1 receptor (CB1R) and a decreased mu opioid receptor (MOR) expression in the prefrontal cortex (PFC). The reinstatement of CCP in females was associated with a decreased MOR expression, but no changes were detected in CB1R in the hippocampus (HIP). Moreover, CBD administration during extinction significantly potentialized the reduced MOR expression in the PFC of males and showed a tendency to potentiate the reduced MOR in the HIP of females. Additionally, CBD reversed OXY-induced deficits of recognition memory only in males. These results suggest that CBD could reduce reinstatement to OXY seeking after a period of abstinence in adolescent male but not female rats. However, more investigation is required.

Funder

Statutory Funds of the Medical University of Lublin

Publisher

MDPI AG

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