Administration of Haloperidol and Risperidone After Neurobehavioral Testing Hinders the Recovery of Traumatic Brain Injury-induced Deficits

Aims: Agitation and aggression are common behavioral sequelae of traumatic brain injury (TBI). The management of these symptoms is critical for effective patient care and therefore antipsychotics are routinely administered even though the benefits vs. risks of this approach on functional outcome after TBI are unclear. A recent study from our group revealed that both haloperidol and risperidone impaired recovery when administered prior to testing. However, the results may have been confounded by drug-induced sedation. Hence, the current study reevaluated the behavioral effects of haloperidol and risperidone when provided after daily testing, thus circumventing the potential sedative effect.

Main Methods: Fifty-four isoflurane-anesthetized male rats received a cortical impact or sham injury and then were randomly assigned to three TBI and three sham groups that received haloperidol (0.5 mg/kg), risperidone (0.45 mg/kg), or vehicle (1.0 mL/kg). Treatments began 24 h after surgery and were administered (i.p.) every day thereafter for 19 days. Motor and cognitive function was assessed on post-operative days 1-5 and 14-19, respectively. Hippocampal CA(1)/CA(3) neurons and cortical lesion volume were quantified at 3 weeks.

Key Findings: Only risperidone delayed motor recovery, but both antipsychotics impaired spatial learning relative to vehicle (p<0.05). Neither swim speed nor histological outcomes were affected. No differences were observed between the haloperidol and risperidone groups in any task.

Significance: These data support our previous finding that chronic haloperidol and risperidone hinder the recovery of TBI-induced deficits, and augment those data by demonstrating that the effects are not mediated by drug-induced sedation.