Chronic administration of antipsychotics impede behavioral recovery after experimental traumatic brain injury.
Antipsychotics are often administered to traumatic brain injured (TBI) patients as a means of controlling agitation, albeit the rehabilitative consequences of this intervention are not well known. Hence, the goal of this study was to evaluate the effects of risperidone (RISP) and haloperidol (HAL) on behavioral outcome after experimental TBI. Anesthetized rats received either a cortical impact or sham injury and then were randomly assigned to five TBI (RISP 0.045mg/kg, RISP 0.45mg/kg, RISP 4.5mg/kg, HAL 0.5mg/kg and VEHicle 1mL/kg) and three Sham (RISP 4.5mg/kg, HAL 0.5mg/kg and VEH 1mL/kg) groups. Treatments began 24h after surgery and were provided once daily for 19 days. Behavior was assessed with established motor (beam-balance/walk) and cognitive (spatial learning/memory in a water maze) tasks on post-operative days 1-5 and 14-19, respectively. RISP and HAL delayed motor recovery, impaired the acquisition of spatial learning, and slowed swim speed relative to VEH in both TBI and sham groups. These data indicate that chronic administration of RISP and HAL impede behavioral recovery after TBI and impair performance in uninjured controls.
Kline
Anthony E
AE
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, USA. klineae@upmc.edu
Hoffman
Ann N
AN
Cheng
Jeffrey P
JP
Zafonte
Ross D
RD
Massucci
Jaime L
JL
D000374:Aggression / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects*; D001930:Brain Injuries / Q000523:psychology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011595:Psychomotor Agitation / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D018967:Risperidone / Q000494:pharmacology; D013028:Space Perception / Q000187:drug effects; D013550:Swimming / Q000502:physiology
D014150:Antipsychotic Agents; D006220:Haloperidol; D018967:Risperidone