Adolescent gamma-hydroxybutyric acid exposure decreases cortical N-methyl-D-aspartate receptor and impairs spatial learning

Pharmacol Biochem Behav. 2004 Dec;79(4):701-8. doi: 10.1016/j.pbb.2004.09.022.


gamma-hydroxybutyric acid (GHB), which belongs to the class of substances referred to as "club drugs", is abused for its euphoric, sedative and anabolic effects. GHB use and abuse is most prevalent among adolescents and young adults. In almost all cases of GHB abuse, subjects report of amnesia. Behavioral effects of GHB in animals, particularly on learning and memory are not known. In this study, effects of GHB exposure on spatial learning and memory in adolescent rats were tested using the Morris water maze (MWM). Adolescent male rats were treated with a single daily injection of one of three doses of GHB for 5 days; control rats received equivalent volumes of saline. GHB-treated rats took longer and swam greater distances to find the hidden platform than control rats. Swim speed in GHB-treated rats was no different from that in vehicle-treated rats. In the probe trial, adolescent rats exposed to GHB spent less time in the target quadrant than control rats. In the visual task, drug-treated rats did not perform any differently than control rats. Brain regions from GHB-exposed and saline-treated rats were examined for N-methyl-D-aspartate (NMDA) receptor changes using [3H]MK-801 binding as a biochemical marker for NMDA channel function. [3H]MK-801 binding in the frontal cortex was significantly reduced compared to saline-treated controls. Together, these data indicate that GHB exposure in adolescent rats negatively impacts spatial learning and this is associated with altered regulation of cortical NMDA receptor.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Dose-Response Relationship, Drug
  • Male
  • Maze Learning / drug effects*
  • Maze Learning / physiology
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Sodium Oxybate / pharmacology*
  • Spatial Behavior / drug effects*
  • Spatial Behavior / physiology


  • Receptors, N-Methyl-D-Aspartate
  • Sodium Oxybate