Δ(9)Tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques.

M J Wright; Sophia A. Vandewater; L H Parsons; Michael A. Taffe

doi:10.1016/j.neuroscience.2013.01.018

Δ(9)Tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques.

M J Wright, Sophia A. Vandewater, L H Parsons, Michael A. Taffe

Neuroscience April 3, 2013 DOI: 10.1016/j.neuroscience.2013.01.018 (opens in new tab)

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Characteristics	Controlled laboratory study Randomized Peer reviewed
Population	Adult male rhesus monkeys
Intervention	Δ(9)tetrahydrocannabinol (Δ(9)THC)
Dose	0.1-0.5 mg/kg, i.m.
Topics	Cannabis
Key points	THC increased errors-to-criterion in reversal learning dose-dependently, did not affect extradimensional shifts, and impaired spatial delayed-response performance in a retention-interval-dependent manner, suggesting greater sensitivity of orbitofrontal-mediated tasks.

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 Δ(9)tetrahydrocannabinol (Δ(9)THC), the major psychoactive constituent of marijuana. Controlled laboratory studies in nonhuman primates provide mixed evidence for specific effects of Δ(9)THC 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 0.1-0.5mg/kg Δ(9)THC, i.m., in randomized order and evaluated on the behavioral measures. Peak plasma levels of Δ(9)THC were observed 30min after 0.2mg/kg (69±29ng/ml) and 60min after 0.5mg/kg (121±23ng/ml) was administered and behavioral effects on a bimanual motor task persisted for up to 2h after injection. An increase in errors-to-criterion (ETC) associated with reversal learning was further increased by Δ(9)THC in a dose-dependent manner. The increase in ETC associated with extradimensional shifts was not affected by Δ(9)THC. Spatial delayed-response performance was impaired by Δ(9)THC in a retention-interval-dependent manner. Overall the pattern of results suggests a more profound effect of Δ(9)THC on tasks mediated by orbitofrontal (reversal learning) versus dorsolateral (extradimensional shifts) prefrontal mechanisms.

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