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Δ9-Tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism

Abstract

The purpose of the present study was to investigate whether the cannabinoid and cholinergic systems impair working memory through a common mechanism. This hypothesis was tested by examining whether the cannabinoid antagonist SR141716A would ameliorate radial-arm performance deficits caused by either the naturally occurring cannabinoid, Δ9-THC, or scopolamine, a muscarinic antagonist. In addition, we evaluated whether the cholinesterase inhibitor, physostigmine, would prevent Δ9-THC-induced impairment of spatial memory. Finally, because the locomotor suppressive effects of cannabinoids may decrease radial arm choice accuracy independent of a direct effect on memory, we examined the impact of increasing the intertrial error on radial arm choice accuracy. As previously reported, Δ9-THC impaired maze performance (ED50=3.0 mg/kg). Increasing the intertrial interval from 5 s to 30 s resulted in a three-fold increase in the amount of time required to complete the maze without affecting choice accuracy. Importantly, SR141716A prevented Δ9-THC-induced deficits in radial-arm choice accuracy in a dose-dependent manner (AD50=2.4 mg/kg); however, the cannabinoid antagonist failed to improve the disruptive effects of scopolamine. Conversely, physostigmine failed to improve performance deficits produced by Δ9-THC. These data provide strong evidence that Δ9-THC impairs working memory through direct action at cannabinoid receptors. Moreover, these results suggest that scopolamine and Δ9-THC do not impair spatial memory in a common serial pathway, though they may converge on a third neurochemical system.

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Correspondence to A. H. Lichtman.

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Lichtman, A.H., Martin, B.R. Δ9-Tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism. Psychopharmacology 126, 125–131 (1996). https://doi.org/10.1007/BF02246347

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Key words

  • Radial-arm maze
  • Δ9-Tetrahydrocannabinol (Δ9-THC)
  • Scopolamine
  • Physostigmine
  • SR141716A
  • Cannabinoid antagonist
  • Working memory