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

Peruzzi, Philippe1,2; Borredon, Josiane1; Seylaz, Jacques1; Lacombe, Pierre1

Neurophysiology, Basic and Clinical

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.

1Laboratoire de Recherches Cérébrovasculaires, CNRS UA 641, Université Paris VII, IFR 6, Circulation Lariboisière, Faculté de Médecine Lariboisière-Saint Louis, 10 Avenue de Verdun, 75010 Paris, France

2Corresponding Author: Philippe Peruzzi

ACKNOWLEDGEMENTS: The authors are grateful to Dr Gabrielle Bitan from Parke-Davis laboratory (France) for the generous gift of tacrine, and to Dr Kamel Kacem and Marie-Hélène Bassant for help with the histochemical study. This work was supported by grants from the Centre National de la Recherche Scientifique (UA 641) and the Université Paris 7-Denis Diderot.

Received 23 July 1996; accepted 18 September 1996

© Lippincott-Raven Publishers.