1. Effects of acute and repeated dosing of the synthetic cannabinoid CP55,940 on intracranial self-stimulation in mice.
- Author
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Grim TW, Wiebelhaus JM, Morales AJ, Negus SS, and Lichtman AH
- Subjects
- Animals, Brain drug effects, Catalepsy chemically induced, Conditioning, Operant drug effects, Cyclohexanols antagonists & inhibitors, Dose-Response Relationship, Drug, Drug Tolerance, Male, Medial Forebrain Bundle physiology, Mice, Piperidines pharmacology, Pyrazoles pharmacology, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Rimonabant, Cyclohexanols pharmacology, Receptor, Cannabinoid, CB1 agonists, Reward, Self Stimulation drug effects
- 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., (Published by Elsevier Ireland Ltd.)
- Published
- 2015
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