Neurochemical stimulation of the rat substantia innominata increases cerebral blood flow (but not glucose use) through the parallel activation of cholinergic and non-cholinergic pathways

Neurochemical activation of the substantia innominata (SI) in the rat, thro ugh the direct injection of the cholinergic agonist carbachol, has been rep orted to induce large increases in cerebral blood flow (CBF) throughout cor tical and subcortical projection regions. The present study aimed to determ ine whether the vasomotor responses to cholinergic stimulation of the SI we re, or were not, the consequence of an increase in metabolic activity. To t his end, coupled measurements of CBF and cerebral glucose use (CGU) were un dertaken during carbachol-elicited stimulation of the SI. Infusion of carba chol into the basal forebrain induced significant CBF increases in several ipsilateral cortical and subcortical areas including the amygdala. In contr ast, CGU increased only in the ipsilateral amygdala and SI. Thus, we tested the hypothesis of a direct neurogenic, rather than metabolic, contribution of the basalocortical system. In this respect, carbachol-elicited stimulat ion resulted in significant increases in extracellular acetylcholine concen trations in the ipsilateral parietal cortex; systemic pretreatment with the muscarinic receptor antagonist scopolamine completely abolished the increa se in cortical CBF elicited by cholinergic stimulation of the SI in the ips ilateral frontoparietal motor cortex while it failed to affect the increase observed in the ipsilateral temporal cortex. Several conclusions can be dr awn from the present study. The stimulation of the SI by carbachol induces an increase in CBF that can be dissociated from changes in underlying gluco se metabolism. Secondly, these induced changes in cortical CBF are parallel ed by an increase in acetylcholine release. Lastly, the failure of scopolam ine to block the flow response in all cortical regions would suggest that S I stimulation will evoke the release of vasodilatatory neurotransmitter(s) as well as acetylcholine itself. (C) 1999 Elsevier Science B.V. All rights reserved.