Lack of behavioral sensitization after repeated exposure to THC in mice and comparison to methamphetamine.
Stephen A Varvel, Billy R Martin, Aron H Lichtman
Psychopharmacology September 2007 DOI: 10.1007/s00213-007-0811-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Institute of Cancer Research (ICR) mice and Sprague-Dawley rats |
| Interventions | Delta(9)-tetrahydrocannabinol (THC) Methamphetamine |
| Topics | Cannabis |
| Key findings | Methamphetamine produced robust dose-dependent behavioral sensitization after intermittent treatment, whereas THC did not produce sensitization under any of the various protocols tested. The authors suggest that repeated THC treatment is less likely than other drugs of abuse to produce behavioral sensitization, and that this phenomenon may only occur under very particular conditions, raising doubts about its relevance to chronic cannabis users. |
Abstract
Recent evidence has provided support for the incentive-sensitization model of addiction, where repeated stimulation of neural reward circuits leads to a long-lasting sensitization of mesolimbic dopaminergic activity. This phenomenon has been demonstrated with many drugs of abuse, most often by measuring progressively increased activating effects of drugs on locomotor activity, thought to reflect an underlying neural sensitization. Whether cannabinoids, and in particular Delta(9)-tetrahydrocannabinol (THC), produce similar effects in this model is somewhat controversial, with mixed evidence in the literature. These experiments were conducted to determine whether behavioral sensitization could be established in mice after repeated exposure to THC. Sensitization to repeated methamphetamine treatment was used as a positive control. The effects of acute and repeated intermittent (every 3-4 days) treatment with THC or methamphetamine on locomotor activity were determined in Institute of Cancer Research (ICR) mice. Additional experiments with THC employed a dosing regimen that increased the number of injections, controlled for behavioral tolerance, examined different aspects of behavior, and used a different species (Sprague-Dawley rats). Both methamphetamine and THC acutely increased activity. A robust dose-dependent sensitization was observed after intermittent treatment with methamphetamine but not with THC. Additionally, no evidence for behavioral sensitization to the effects of THC was found with any of the various protocols. These data suggest that repeated THC treatment is less likely to produce behavioral sensitization than are other drugs of abuse. It appears that this phenomenon may only occur under very particular conditions, which raises doubts about its relevance to chronic cannabis users.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 2
- Interactions between cannabidiol and Δ9-THC following acute and repeated dosing: Rebound hyperactivity, sensorimotor gating and epigenetic and neuroadaptive changes in the mesolimbic pathway. European Neuropsychopharmacology February 2017
- Behavioral pharmacology of cannabinoids with a focus on preclinical models for studying reinforcing and dependence-producing properties. Current Drug Abuse Reviews November 2008