Haloperidol, but not olanzapine, impairs cognitive performance after traumatic brain injury in rats

Am J Phys Med Rehabil. 2003 Nov;82(11):871-9. doi: 10.1097/01.PHM.0000091982.33232.CB.


Objective: Traumatic brain injury can cause a variety of impairments, including persistent alterations in personality, mood, and cognition. Antipsychotic agents are frequently used to treat pathologic behaviors in traumatic brain injury patients, but the influence of prolonged administration of such drugs on cognition after injury is unknown. The effects of two antipsychotic drugs on cognitive recovery after traumatic brain injury were assessed using the fluid percussion model in rats.

Design: The typical antipsychotic, haloperidol, and the third-generation antipsychotic, olanzapine, were administered via intraperitoneal injection beginning 24 hr after injury and continuing daily for the duration of the study. Morris water maze performance was assessed on days 11-15 postinjury.

Results: Haloperidol, an antagonist acting on D2-like dopamine receptors, exacerbated the cognitive deficits induced by injury, as injured rats treated with 0.30 mg/kg haloperidol performed worse in the Morris water maze than injured rats treated with vehicle.

Conclusions: Our results demonstrate the importance of the D2 receptor in cognitive recovery after traumatic brain injury. Also, the data illustrate that some classes of antipsychotic drugs may influence cognitive recovery, and further research is needed to determine the optimal pharmacologic treatment of aggression, agitation, and other pathologic behaviors in patients with traumatic brain injury.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Antipsychotic Agents / pharmacology*
  • Benzodiazepines
  • Brain Injuries / complications*
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Dopamine Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Haloperidol / pharmacology*
  • Injections, Intraperitoneal
  • Male
  • Maze Learning / drug effects
  • Olanzapine
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Swimming


  • Antipsychotic Agents
  • Dopamine Antagonists
  • Benzodiazepines
  • Pirenzepine
  • Haloperidol
  • Olanzapine