Delta 9-tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism

Psychopharmacology (Berl). 1996 Jul;126(2):125-31. doi: 10.1007/BF02246347.


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, delta 9-THC, or scopolamine, a muscarinic antagonist. In addition, we evaluated whether the cholinesterase inhibitor, physostigmine, would prevent delta 9-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, delta 9-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 delta 9-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 delta 9-THC. These data provide strong evidence that delta 9-THC impairs working memory through direct action at cannabinoid receptors. Moreover, these results suggest that scopolamine and delta 9-THC do not impair spatial memory in a common serial pathway, though they may converge on a third neurochemical system.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Dronabinol / pharmacology*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Physostigmine / pharmacology
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cannabinoid
  • Receptors, Drug / drug effects*
  • Receptors, Drug / physiology
  • Rimonabant
  • Scopolamine / pharmacology


  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Dronabinol
  • Physostigmine
  • Scopolamine
  • Rimonabant