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 markedly increased immediately after TBI, the present s tudy was undertaken to evaluate the effect of modulating these early c hanges in NE metabolism on recovery of function. Rats were pretrained on a modified beam walking task. Thirty minutes prior to unilateral so matosensory cortex contusion they were treated with a NE reuptake bloc ker [desmethylimipramine (DMI); 10 mg/kg, ip, n = 6] or an alpha(1)-ad renoreceptor antagonist [prazosin (PRZ); 3 mg/kg, ip, n = 6]. PRZ pret reatment markedly worsened beam walking performance throughout the 3 w eeks following injury, whilst DMI pretreatment did not affect performa nce compared to injured controls (n = 4). Despite the marked behaviora l deficits, PRZ-treated animals showed no apparent worsening of histol ogical damage (n = 11 per group) and lesion size was the same in all g roups. In separate experiments (n = 4 per group), PRZ lowered basal bl ood pressure and prevented the rise in pressure immediately following TBI. However, blood pressures in the three groups came to the same lev el within 20 sec following TBI. This suggests that the action of PRZ w as not simply due to hypotension-induced ischemia. It is possible that blockade of al-adrenoreceptors in the immediate posttrauma period lea ds to enhancement of excitatory neurotransmission, which exacerbates b ehavioral deficits.