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


METHODS
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.
Wilson
Margaret S
MS
Department of Psychology, Virginia Commonwealth University, Richmond, USA.
Gibson
Cynthia J
CJ
Hamm
Robert J
RJ
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D001930:Brain Injuries / Q000150:complications*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D001569:Benzodiazepines; D010890:Pirenzepine; D006220:Haloperidol; D000077152:Olanzapine