Prolonged cannabinoid treatment results in spatial working memory deficits and impaired long-term potentiation in the CA1 region of the hippocampus in vivo

Eur J Neurosci. 2004 Aug;20(3):859-63. doi: 10.1111/j.1460-9568.2004.03522.x.


Adult male Long-Evans rats were administered the potent cannabinoid 1 receptor agonist HU-210 (100 microg/kg, i.p.) for 15 days continuously and their performance on a matching-to-place version of the Morris water maze was subsequently evaluated. Overall, experimental animals performed significantly worse initially on the reference memory component of this task, but their performance improved over 5 days until it was indistinguishable from that of control animals. Animals given HU-210 did not exhibit working memory impairments at short intertrial delays (30 s); however, significant impairments were observed in learning performance with longer intertrial delays (300 s). In vivo electrophysiological analyses revealed that long-term potentiation in the CA1 region of the hippocampus was significantly impaired following the administration of HU-210 for 15 days. These results indicate that long-term cannabinoid exposure can produce marked deficits in reference and working memory performance, and also impair hippocampal synaptic plasticity in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Cannabinoids / adverse effects
  • Cannabinoids / pharmacology*
  • Dronabinol / adverse effects
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology*
  • Electrophysiology / methods
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Long-Term Potentiation / drug effects*
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / chemically induced*
  • Memory, Short-Term / drug effects*
  • Rats
  • Rats, Long-Evans
  • Reaction Time / drug effects
  • Time
  • Time Factors


  • Cannabinoids
  • Dronabinol
  • HU 211