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. 2017 Mar 1;20(3):269-278.
doi: 10.1093/ijnp/pyw102.

Attenuation of Cocaine-Induced Conditioned Place Preference and Motor Activity via Cannabinoid CB2 Receptor Agonism and CB1 Receptor Antagonism in Rats

Foteini Delis  1 , Alexia Polissidis  1   2 , Nafsika Poulia  1 , Zuzana Justinova  3 , George G Nomikos  4 , Steven R Goldberg  3 , Katerina Antoniou  1
Affiliations

Attenuation of Cocaine-Induced Conditioned Place Preference and Motor Activity via Cannabinoid CB2 Receptor Agonism and CB1 Receptor Antagonism in Rats

Foteini Delis et al. Int J Neuropsychopharmacol. .

Abstract

Background: Studies have shown the involvement of cannabinoid (CB) receptors in the behavioral and neurobiological effects of psychostimulants. Most of these studies have focused on the role of CB1 receptors in the psychostimulant effects of cocaine, while very few have investigated the respective role of CB2 receptors. Further studies are warranted to elucidate the extent of CB receptor involvement in the expression of cocaine-induced effects.

Methods: The role of CB1 and CB2 receptors in the rewarding and motor properties of cocaine was assessed in conditioned place preference, conditioned motor activity, and open field activity in rats.

Results: The CB1 receptor antagonist rimonabant (3 mg/kg) decreased the acquisition and the expression of conditioned place preference induced by cocaine (20 mg/kg). Rimonabant inhibited cocaine-elicited conditioned motor activity when administered during the expression of cocaine-induced conditioned place preference. Rimonabant decreased ambulatory and vertical activity induced by cocaine. The CB2 receptor agonist JWH-133 (10 mg/kg) decreased the acquisition and the expression of cocaine-induced conditioned place preference. JWH-133 inhibited cocaine-elicited conditioned motor activity when administered during the acquisition and the expression of cocaine-induced conditioned place preference. JWH-133 decreased ambulatory activity and abolished vertical activity induced by cocaine. The effects of JWH-133 on cocaine conditioned and stimulated responses were abolished when the CB2 receptor antagonist/inverse agonist AM630 (5 mg/kg) was preadministered.

Conclusions: Cannabinoid CB1 and CB2 receptors modulate cocaine-induced rewarding behavior and appear to have opposite roles in the regulation of cocaine's reinforcing and psychomotor effects.

Keywords: CB1; CB2; cocaine; conditioned place preference; motor activity.

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Figures

Figure 1.
Figure 1.
Effects of rimonabant on cocaine-induced conditioned place preference (CPP) acquisition (A) and expression (B). The bars represent the mean + SEM of the difference between time spent in the drug-paired and vehicle-paired chambers on test day. COC, cocaine 20 mg/kg; RIM, rimonabant 3 mg/kg. *Compared with corresponding vehicle treatment, C compared with cocaine (VEH2+COC).
Figure 2.
Figure 2.
Effects of JWH-133 on cocaine-induced conditioned place preference (CPP) acquisition (A) and expression (B). The bars represent the mean + SEM of the difference between time spent in drug-paired and vehicle-paired chambers on test day. COC, cocaine, 20 mg/kg; JWH, 10 mg/kg JWH-133; AM, 5 mg/kg AM630. * compared with corresponding vehicle treatment, C compared with cocaine (VEH1+VEH2+COC).
Figure 3.
Figure 3.
Effects of rimonabant on cocaine-elicited conditioned motor activity. (A) Motor activity in drug-paired and unpaired chambers on test day, after pre-pairing administration of rimonabant. (B) Total motor activity (drug-paired + unpaired chambers) on test day, after pre-pairing administration of rimonabant. (C) Motor activity in drug-paired and unpaired chambers on test day, after rimonabant administration on test day. (D) Total motor activity (drug-paired + unpaired chambers) on test day, after rimonabant administration on test day. The bars represent mean + SEM; COC, 20 mg/kg cocaine; RIM, 3 mg/kg rimonabant. ^ compared with unpaired chamber.
Figure 4.
Figure 4.
Effects of JWH-133 on cocaine-elicited conditioned motor activity. (A) Motor activity in drug-paired and unpaired chambers on test day, after pre-pairing administration of JWH-133 and/or AM630 during conditioning. (B) Total motor activity (drug-paired + unpaired chambers) on test day, after pre-pairing administration of JWH-133 and/or AM630 during conditioning. (C) Motor activity in drug-paired and unpaired chambers on test day, after JWH-133 and/or AM630 administration on test day. (D) Total motor activity (drug-paired + unpaired chambers) on test day, after JWH-133 and/or AM630 administration on test day. COC, 20 mg/kg cocaine; JWH, 10 mg/kg JWH-133; AM630, 5 mg/kg AM. ∧ compared with unpaired chamber.
Figure 5.
Figure 5.
Effects of rimonabant on cocaine-stimulated motor activity. (A) Horizontal motor activity. The bars represent mean + SEM of the ambulatory distance (cm). (B) Vertical motor activity. The bars represent mean + SEM of the number of vertical counts. COC, 20 mg/kg cocaine; RIM, 3 mg/kg rimonabant. *Compared with respective vehicle treatment, C compared with cocaine (VEH2+COC).
Figure 6.
Figure 6.
Effects of JWH-133 on cocaine-stimulated motor activity. (A) Horizontal motor activity. The bars represent mean + SEM of the ambulatory distance (cm). (B) Vertical motor activity. The bars represent mean + SEM of the number of vertical counts. COC, 20 mg/kg cocaine; JWH, 10 mg/kg JWH-133; AM, 5 mg/kg AM630. *Compared with vehicle (VEH1+VEH2+SAL) and with JWH (VEH1+JWH+SAL) treatments, C compared with cocaine (VEH1+VEH2+COC), + compared with AM+JWH+COC treatment, ● compared with vehicle (VEH1+VEH2+SAL), JWH (VEH1+JWH+SAL), and VEH1+JWH+COC treatments.
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