delta(9)-Tetrahydrocannabinol-dependent mice undergoing withdrawal display impaired spatial memory.
Laura E Wise, Stephen A Varvel, Dana E Selley, Jason M Wiebelhaus, Kelly A Long, Lisa S Middleton, Laura J Sim-Selley, Aron H Lichtman
Psychopharmacology October 2011 DOI: 10.1007/s00213-011-2305-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | THC-dependent mice |
| Intervention | Rimonabant |
| Measures | Morris water maze |
| Topics | Cannabis |
| Key findings | Rimonabant precipitated spatial memory deficits in THC-dependent mice at doses lower than those required to precipitate somatic withdrawal, while cued-task performance remained near perfect. Rimonabant also increased adenylyl cyclase activity in cerebellar but not hippocampal membranes. The authors propose that spatial memory impairment is a particularly sensitive component of cannabinoid withdrawal, potentially mediated by compensatory cerebellar changes. |
Abstract
Cannabis users display a constellation of withdrawal symptoms upon drug discontinuation, including sleep disturbances, irritability, and possibly memory deficits. In cannabinoid-dependent rodents, the CB(1) antagonist rimonabant precipitates somatic withdrawal and enhances forskolin-stimulated adenylyl cyclase activity in cerebellum, an effect opposite that of acutely administered ∆(9)-tetrahydrocannabinol (THC), the primary constituent in cannabis. Here, we tested whether THC-dependent mice undergoing rimonabant-precipitated withdrawal display short-term spatial memory deficits, as assessed in the Morris water maze. We also evaluated whether rimonabant would precipitate adenylyl cyclase superactivation in hippocampal and cerebellar tissue from THC-dependent mice. Rimonabant significantly impaired spatial memory of THC-dependent mice at lower doses than those necessary to precipitate somatic withdrawal behavior. In contrast, maze performance was near perfect in the cued task, suggesting sensorimotor function and motivational factors were unperturbed by the withdrawal state. Finally, rimonabant increased adenylyl cyclase activity in cerebellar, but not in hippocampal, membranes. The memory disruptive effects of THC undergo tolerance following repeated dosing, while the withdrawal state leads to a rebound deficit in memory. These results establish spatial memory impairment as a particularly sensitive component of cannabinoid withdrawal, an effect that may be mediated through compensatory changes in the cerebellum.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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