Alpha 1-adrenoceptor blockade increases behavioral deficits in traumatic brain injury.

Experimental enhancement of noradrenergic activity following traumatic brain injury (TBI) accelerates behavioral recovery if performed at a time when brain norepinephrine (NE) turnover is decreased. But, since NE turnover is markedely increased immediately after TBI, the present study was undertaken to evaluate the effect of modulating these early changes in NE metabolism on recovery of function. Rats were pretrained on a modified beam walking task. Thirty minutes prior to unilateral somatosensory cortex contusion they were treated with a NE reuptake blocker [desmethy-limipramine (DMI); 10 mg/kg, ip, n = 6] or an alpha 1-adrenoreceptor antagonist [prazosin (PRZ); 3 mg/kg, ip, n = 6]. PRZ pretreatment markedly worsened beam walking performance throughout the 3 weeks following injury, whilst DMI pretreatment did not affect performance compared to injured controls (n = 4). Despite the marked behavioral deficits, PRZ-treated animals showed no apparent worsening of histological damage (n = 11 per group) and lesion size was the same in all groups. In separate experiments (n = 4 per group), PRZ lowered basal blood pressure and prevented the rise in pressure immediately following TBI. However, blood pressures in the three groups came to the same level within 20 sec following TBI. This suggest that the action of PRZ was not simply due to hypotension-induced ischemia. It is possible that blockade of alpha 1-adrenoreceptors in the immediate posttrauma period leads to enhancement of excitatory neurotransmission, which exacerbates behavioral deficits.