Effects of Adolescent Cannabinoid Self-Administration in Rats on Addiction-Related Behaviors and Working Memory.
Erin K Kirschmann, Michael W Pollock, Vidhya Nagarajan, Mary M Torregrossa
Neuropsychopharmacology April 2017 DOI: 10.1038/npp.2016.178 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical rodent study Peer reviewed |
|---|---|
| Population | Adolescent male rats |
| Interventions | WIN55 212-2 |
| Duration | 2-h or 6-h self-administration sessions/day during adolescence; 21 days of abstinence before reinstatement testing; cognitive testing in adulthood |
| Measures | delay-match-to-sample working memory task, spatial recognition task |
| Topics | Addiction |
| Key points | Adolescent male rats that self-administered the synthetic cannabinoid WIN55,212-2 showed cue-induced reinstatement that increased after 21 days of abstinence, and in adulthood performed better on a working memory task than sucrose controls, with altered prefrontal GABAergic and glutamatergic protein expression. Self-administered WIN produced no long-term cognitive deficits, while experimenter-administered WIN caused acute short-term memory deficits that recovered with abstinence. |
Abstract
Use of marijuana (Cannabis sativa) often begins in adolescence, and heavy adolescent marijuana use is often associated with impaired cognitive function in adulthood. However, clinical reports of long-lasting cognitive deficits, particularly in subjects who discontinue use in adulthood, are mixed. Moreover, dissociating innate differences in cognitive function from cannabis-induced deficits is challenging. Therefore, the current study sought to develop a rodent model of adolescent cannabinoid self-administration (SA), using the synthetic cannabinoid receptor agonist WIN55,212-2 (WIN), in order to assess measures of relapse/reinstatement of drug seeking and long-term effects on cognitive function assessed in a delay-match-to-sample working memory task and a spatial recognition task. Adolescent male rats readily self-administered WIN in 2-h or 6-h sessions/day, but did not demonstrate an escalation of intake with 6-h access. Rats exhibited significant cue-induced reinstatement of WIN seeking that increased with 21 days of abstinence (ie, 'incubation of craving'). Cognitive testing occurred in adulthood under drug-free conditions. Both 2-h and 6-h adolescent WIN SA groups exhibited significantly better working memory performance in adulthood relative to sucrose SA controls, and performance was associated with altered expression of proteins regulating GABAergic and glutamatergic signaling in the prefrontal cortex. Self-administered WIN did not produce either acute or chronic effects on short-term memory, but experimenter administration of WIN in adolescence, at doses previously reported in the literature, produced acute deficits in short-term memory that recovered with abstinence. Thus, SA of a rewarding cannabinoid in adolescence does not produce long-term cognitive dysfunction.
Comparable studies
Other preclinical and animal studies on addiction, most cited first.
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| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study | |
| Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Morphine-dependent rats | 1992 | Randomized controlled trial | |
| Structure-based discovery of conformationally selective inhibitors of the serotonin transporter. Mice | 2023 | Computational docking and experimental validation | |
| Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Rats | 2001 | Experimental study |
Citations in the library
Cited by 6
- Disruption of Reelin signaling in a dual-hit mouse model of schizophrenia: impact of postnatal Δ9-tetrahydrocannabinol exposure in a maternal immune activation model Translational Psychiatry July 16, 2026
- Which Came First? Utility of Preclinical Models in Cracking the Chicken-or-Egg Relationship between Cannabis Use and Schizophrenia Current Addiction Reports February 27, 2026
- Endocannabinoid system contributions to sex-specific adolescent neurodevelopment. Progress in Neuro-Psychopharmacology and Biological Psychiatry March 8, 2022
- Dos(e)Age: Role of Dose and Age in the Long-Term Effect of Cannabinoids on Cognition Molecules February 1, 2022
- The Effects of Cannabinoids on Executive Functions: Evidence from Cannabis and Synthetic Cannabinoids—A Systematic Review Brain Sciences February 27, 2018
and 1 more in the library
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- Repeated Δ9-tetrahydrocannabinol exposure in adolescent monkeys: persistent effects selective for spatial working memory. American Journal of Psychiatry April 2014
- Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid. Nature Neuroscience November 2013
- Delay- and dose-dependent effects of Δ⁹-tetrahydrocannabinol administration on spatial and object working memory tasks in adolescent rhesus monkeys. Neuropsychopharmacology May 2012
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