Article

Δ9Tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques

Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA
Neuroscience (Impact Factor: 3.36). 01/2013; 235:51–58. DOI: 10.1016/j.neuroscience.2013.01.018

ABSTRACT

Expansion of medical marijuana use in the US and the recently successful decriminalization of recreational marijuana in two States elevates interest in the specific cognitive effects of Δ9tetrahydrocannabinol (Δ9THC), the major psychoactive constituent of marijuana. Controlled laboratory studies in nonhuman primates provide mixed evidence for specific effects of Δ9THC in learning and memory tasks, with a suggestion that frontal-mediated tasks may be the most sensitive. In this study, adult male rhesus monkeys were trained on tasks which assess reversal learning, extradimensional attentional shift learning and spatial delayed-response. Subjects were challenged with 0.1–0.5 mg/kg Δ9THC, i.m., in randomized order and evaluated on the behavioral measures. Peak plasma levels of Δ9THC were observed 30 min after 0.2 mg/kg (69 ± 29 ng/ml) and 60 min after 0.5 mg/kg (121 ± 23 ng/ml) was administered and behavioral effects on a bimanual motor task persisted for up to 2 h after injection. An increase in errors-to-criterion (ETC) associated with reversal learning was further increased by Δ9THC in a dose-dependent manner. The increase in ETC associated with extradimensional shifts was not affected by Δ9THC. Spatial delayed-response performance was impaired by Δ9THC in a retention-interval-dependent manner. Overall the pattern of results suggests a more profound effect of Δ9THC on tasks mediated by orbitofrontal (reversal learning) versus dorsolateral (extradimensional shifts) prefrontal mechanisms.

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    • "It is a cognitive function that is frequently reported to be affected by drug use. Preclinical research has revealed that cannabis and cocaine are associated with impaired reversal learning (Egerton et al. 2005; Sokolic et al. 2011; Wright et al. 2013; McCracken and Grace 2013; Schoenbaum et al. 2004). Furthermore, chronic cocaine use in human addicted "
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    • "However, similar to Y-maze performance, there was no effect of chronic CP treatment, strengthening the selectivity of its action on PPI. Thus, although previous studies have shown involvement of both the endocannabinoid system and BDNF in memory formation and consolidation (Papaleo et al., 2011; Panlilio et al., 2012; De Bitencourt et al., 2013; Wright et al., 2013), in our protocol including chronic CP treatment followed by a 2-week washout, there were no such effects. Future studies could include the acute effects of cannabinoid receptor stimulation on memory function in BDNF HET mice and controls after chronic pre-treatment with CP, similar to the PPI studies presented here. "
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