Article

Antipsychotic drugs (APDs) are used to manage traumatic brain injury
(TBI)-induced behavioral disturbances, such as agitation and aggression. However,
APDs exhibiting D2 receptor antagonism impede cognitive recovery after
experimental TBI. Hence, empirical evaluation of APDs with different mechanistic
actions is warranted. Aripiprazole (ARIP) is a D2 and 5-hydroxytryptamine1A
(5-HT1A) receptor agonist; pharmacotherapies with these properties enhance
cognition after TBI. OBJECTIVE: To test the hypothesis that ARIP would increase
behavioral performance and decrease histopathology after TBI. METHODS: Adult male
rats were subjected to either a controlled cortical impact (CCI)
or sham injury
and then randomly assigned to ARIP (0.1 or 1.0 mg/kg) or VEH (1.0 mL/kg, saline
vehicle) groups. Treatments began 24 hours after surgery and were administered
once daily for 19 days. Motor (beam-balance/beam-walk) and cognitive (Morris
water maze) performance was assessed on postoperative days 1 to 5 and 14 to 19,
respectively, followed by quantification of hippocampal CA1,3 neuron survival and
cortical lesion volume. RESULTS: Beam-balance was significantly improved in the
CCI + ARIP (1.0 mg/kg) group versus CCI + ARIP (0.1 mg/kg) and CCI + VEH (P <
.05). Spatial learning and memory retention were significantly improved in the
CCI + ARIP (0.1 mg/kg) group versus the CCI + ARIP (1.0 mg/kg) and CCI + VEH
groups (P < .05). Both doses of ARIP reduced lesion size and CA3 cell loss versus
VEH (P < .05). Importantly, neither dose of ARIP impeded functional recovery as
previously reported with other APDs. CONCLUSION:
These findings support the
hypothesis and endorse ARIP as a safer APD for alleviating behavioral disturbances after TBI.
CI - (c) The Author(s) 2016.

Langue : ANGLAIS