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Administration of Δ9-Tetrahydrocannabinol (THC) in Adolescent and Adult Mice
Published on: August 1, 2025
delta(9)-Tetrahydrocannabinol-dependent mice undergoing withdrawal display impaired spatial memory
Laura E Wise1, Stephen A Varvel, Dana E Selley
1Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 98061, Richmond, VA 23298, USA.
Psychopharmacology
|May 12, 2011
Summary
Cannabis withdrawal, specifically from delta-9-tetrahydrocannabinol (THC), causes significant short-term spatial memory deficits in mice. These memory impairments are a sensitive indicator of cannabinoid withdrawal, potentially linked to cerebellar changes.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Cannabis use is associated with withdrawal symptoms like sleep disturbances and irritability.
- Cannabinoid receptor 1 (CB(1)) antagonist rimonabant induces withdrawal in cannabinoid-dependent rodents.
- Acute delta-9-tetrahydrocannabinol (THC) has effects opposite to rimonabant on adenylyl cyclase activity.
Purpose of the Study:
- To investigate if THC-dependent mice exhibit spatial memory deficits during rimonabant-induced withdrawal.
- To determine if rimonabant causes adenylyl cyclase superactivation in the hippocampus and cerebellum of THC-dependent mice.
Main Methods:
- Utilized the Morris water maze to assess spatial memory in THC-dependent mice.
- Administered rimonabant to precipitate withdrawal and evaluated behavioral and biochemical changes.
- Measured forskolin-stimulated adenylyl cyclase activity in hippocampal and cerebellar membranes.
Main Results:
- Rimonabant impaired spatial memory at lower doses than those causing somatic withdrawal.
- Performance in a cued task remained intact, indicating preserved sensorimotor function.
- Rimonabant increased adenylyl cyclase activity in cerebellar membranes but not hippocampal membranes.
Conclusions:
- Tolerance to THC's memory effects develops with repeated use.
- Cannabinoid withdrawal results in a rebound memory deficit.
- Spatial memory impairment is a sensitive marker of cannabinoid withdrawal, possibly mediated by cerebellar adaptations.
