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

被引:3
作者
Socha, Justyna [1 ]
Grochecki, Pawel [1 ]
Marszalek-Grabska, Marta [2 ]
Skrok, Aleksandra [1 ]
Smaga, Irena [3 ]
Slowik, Tymoteusz [4 ]
Prazmo, Wojciech [5 ]
Kotlinski, Robert [6 ]
Filip, Malgorzata [3 ]
Kotlinska, Jolanta H. [1 ]
机构
[1] Med Univ Lublin, Dept Pharmacol & Pharmacodynam, Chodzki 4a, PL-20093 Lublin, Poland
[2] Med Univ, Dept Expt & Clin Pharmacol, Jaczewskiego 8b, PL-20090 Lublin, Poland
[3] Polish Acad Sci, Dept Drug Addict Pharmacol, Maj Inst Pharmacol, Smetna 12, PL-31343 Krakow, Poland
[4] Med Univ, Expt Med Ctr, Jaczewskiego 8, PL-20090 Lublin, Poland
[5] Prov Specialist Hosp, Breast Surg Dept, Al Krasnicka 100, PL-20718 Lublin, Poland
[6] Univ Rzeszow, Clin Dept Cardiac Surg, Lwowska 60, PL-35301 Rzeszow, Poland
关键词
oxycodone; cannabidiol; reward; conditioned place preference; MOR; CB1R; adolescent rats; CANNABINOID CB2 RECEPTOR; VENTRAL TEGMENTAL AREA; PREFRONTAL CORTEX; BRAIN REWARD; ALLOSTERIC MODULATOR; DOPAMINE NEURONS; SEX-DIFFERENCES; OPIOID USE; MORPHINE; DEPRESSION;
D O I
10.3390/ijms25126651
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:17
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