Citation

Grim TW, Wiebelhaus JM, Morales AJ, Negus SS, Lichtman AH. Drug Alcohol Depend. 2015; 150: 31-37.

Affiliation

Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, PO Box 980613, Richmond, 23298-0613, VA U.S.A.

Copyright

(Copyright © 2015, Elsevier Publishing)

DOI

10.1016/j.drugalcdep.2015.01.022

PMID

25772438

Abstract

BACKGROUND: Synthetic cannabinoids have emerged as a significant public health concern. To increase the knowledge of how these molecules interact on brain reward processes, we investigated the effects of CP55,940, a high efficacy synthetic CB1 receptor agonist, in a frequency-rate intracranial self-stimulation (ICSS) procedure.

METHODS: The impact of acute and repeated administration (seven days) of CP55,940 on operant responding for electrical brain stimulation of the medial forebrain bundle was investigated in C57BL/6J mice.

RESULTS: CP55,940 attenuated ICSS in a dose-related fashion (ED50 (95% C.L.)=0.15 (0.12-0.18)mg/kg). This effect was blocked by the CB1 receptor antagonist rimonabant. Tolerance developed quickly, though not completely, to the rate-decreasing effects of CP55,940 (0.3mg/kg). Abrupt discontinuation of drug did not alter baseline responding for up to seven days. Moreover, rimonabant (10mg/kg) challenge did not alter ICSS responding in mice treated repeatedly with CP55,940.

CONCLUSIONS: The finding that CP55,940 reduced ICSS in mice with no evidence of facilitation at any dose is consistent with synthetic cannabinoid effects on ICSS in rats. CP55,940-induced ICSS depression was mediated through a CB1 receptor mechanism. Additionally, tolerance and dependence following repeated CP55,940 administration were dissociable. Thus, CP55,940 does not produce reward-like effects in ICSS under these conditions.

Language: en