TACRINE OVERCOMPENSATES FOR THE DECREASED BLOOD-FLOW INDUCED BY BASALFOREBRAIN LESION IN THE RAT

THE effects of tacrine on the cerebral blood flow (CBF) were investiga ted according to an experimental model of the cholinergic hypothesis i n rats with unilateral lesion of the substantia innominata (SI). CBF w as measured 1-2 weeks following SI lesion with ibotenic acid, using th e tissue sampling [C-14]iodoantipyrine technique in three groups of le sioned rats infused i.v. with tacrine at 3 or 8 mg kg(-1) h(-1) or wit h saline. SI lesioning resulted in moderate, significant blood flow de creases in the parietal, frontal and occipital cortical areas. In the intact hemibrain, tacrine at a dose of 3 mg kg(-1) h(-1) had no signif icant effect, but at 8 mg kg(-1) h(-1) tacrine increased the blood flo w in most of the cortical and subcortical regions investigated. The in creases ranged from 21% (hypothalamus) to 101% (parietal cortex) compa red with controls. Tacrine had greater effects in the lesioned hemisph ere, even at the dose of 3 mg kg(-1) h(-1). The flow increases in the frontal or parietal cortex of the lesioned hemisphere were 1.5-3.6 tim es greater than in the intact hemisphere. Thus, in contrast to what wa s expected, tacrine overcompensates for the cerebrovascular effects of SI lesions.