, Volume 140, Issue 1, pp 11–19

The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by Δ9-tetrahydrocannabinol or anandamide

  • P. E. Mallet
  • R. J. Beninger
Original Investigation

DOI: 10.1007/s002130050733

Cite this article as:
Mallet, P. & Beninger, R. Psychopharmacology (1998) 140: 11. doi:10.1007/s002130050733


 The administration of Δ9-tetrahydrocannabinol (THC), the principle psychoactive ingredient in marijuana, or the endogenous cannabinoid anandamide, has been shown to impair recent memory. The purpose of the present investigation was to determine if the cannabinoid CB1 receptor antagonist SR141716A could attenuate THC- or anandamide-induced memory impairment, and to assess the effects on memory of SR141716A alone. Memory was assessed in rats well-trained in a two-component instrumental discrimination task, consisting of a conditional discrimination, and a non-match-to-position to assess recent or working memory. SR141716A (0.0–2.0 mg/kg) had no effect on either the conditional discrimination or the non-match-to-position. However, SR141716A (0.0–2.0 mg/kg) attenuated the memory impairment produced by THC (2.0 or 4.0 mg/kg) as indexed by an enhancement of performance in the non-match-to-position. When administered to rats pretreated with anandamide (2.0 mg/kg), SR141716A (0.0–2.5 mg/kg) impaired performance in the conditional discrimination at the highest dose. This was interpreted as a deficit in some capacity unrelated to memory (e.g., motor impairment). However, lower doses of SR141716A (0.1 and 0.5 mg/kg) attenuated the anandamide-induced impairment of performance in the non-match-to-position without affecting the conditional discrimination. This is the first report that the memory impairment produced by anandamide can be attenuated by a cannabinoid antagonist; results suggest that anandamide-induced memory disruption is mediated by CB1 receptors.

Key words CannabinoidAnandamideSR141716AΔ9-tetrahydrocannabinol (Δ9-THC) Reference memoryWorking memoryConditional discriminationNon-match-to-position

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • P. E. Mallet
    • 1
  • R. J. Beninger
    • 1
  1. 1.Department of Psychology, Queen’s University, Kingston, Ontario, Canada K7L 3N6 e-mail: beninger@psyc.queensu.caCA
  2. 2.Department of Psychiatry, Queen’s University, Kingston, Ontario, Canada K7L 3N6CA