title: Differential effects of delta 9-THC on spatial reference and working memory in mice.
abstract: BACKGROUND
  Marijuana remains the most widely used illicit drug in the U.S., and recent attention has been given to putative therapeutic uses of marijuana and cannabinoid derivatives. Thus, developing a better understanding of delta9-THC (tetrahydrocannabinol)-induced mnemonic deficits is of critical importance.
  
  
  OBJECTIVE
  These experiments were conducted to determine whether delta9-THC has differential effects on spatial reference and working memory tasks, to investigate its receptor mechanism of action, and to compare these effects with those produced by two other compounds--scopolamine and phencyclidine--known to produce mnemonic deficits. In addition, the potency of delta9-THC in these memory tasks was compared with its potency in other pharmacological effects traditionally associated with cannabinoid activity.
  
  
  METHODS
  Two different versions of the Morris water maze were employed: a working memory task and a reference memory task. Other effects of delta9-THC were assessed using standard tests of hypomotility, antinociception, catalepsy, and hypothermia.
  
  
  RESULTS
  delta9-THC disrupted performance of the working memory task (3.0 mg/kg) at doses lower than those required to disrupt performance of the reference memory task (100 mg/kg), or elicit hypomotility, antinociception, catalepsy, and hypothermia. These performance deficits were reversed by SR 141716A. The effects of delta9-THC resembled those of scopolamine, which also selectively disrupted the working maze task. Conversely, phencyclidine disrupted both tasks only at a dose that also produced motor deficits.
  
  
  CONCLUSIONS
  These data indicate that delta9-THC selectively impairs performance of a working memory task through a CB, receptor mechanism of action and that these memory disruptions are more sensitive than other pharmacological effects of delta9-THC.
authors.affiliation: Department of Pharmacology, VCU, Richmond, VA 23298, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Varvel
authors.forename: R J
authors.initials: RJ
authors.lastname: Hamm
authors.forename: B R
authors.initials: BR
authors.lastname: Martin
authors.forename: A H
authors.initials: AH
authors.lastname: Lichtman
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology
chemical_list: D006213:Hallucinogens; D018727:Muscarinic Antagonists; D011619:Psychotropic Drugs; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; D012601:Scopolamine; D010622:Phencyclidine