Tacrine overcompensates for the decreased blood flow induced by basal forebrain lesion in the rat

The effects of tacrine on the cerebral blood flow (CBF) were investigated according to an experimental model of the cholinergic hypothesis in rats with unilateral lesion of the substantia innominata (SI). CBF was measured 1-2 weeks following SI lesion with ibotenic acid, using the tissue sampling [14C]iodoantipyrine technique in three groups of lesioned rats infused i.v. with tacrine at 3 or 8 mg kg-1 h-1 or with saline. SI lesioning resulted in moderate, significant blood flow decreases in the parietal, frontal and occipital cortical areas. In the intact hemi-brain, tacrine at a dose of 3 mg kg-1 h-1 had no significant effect, but at 8 mg kg-1 h-1 tacrine increased the blood flow in most of the cortical and subcortical regions investigated. The increases ranged from 21% (hypothalamus) to 101% (parietal cortex) compared with controls. Tacrine had greater effects in the lesioned hemisphere, 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 times greater than in the intact hemisphere. Thus, in contrast to what was expected, tacrine overcompensates for the cerebrovascular effects of SI lesions.