Interactions of cholinergic and glutamatergic neuronal systems in the functional activation of cerebral blood flow response: a PET study in unanesthetized monkeys

Abstract

The effects of somatosensory stimulation on the regional cerebral blood flow (rCBF) response were studied in unanesthetized monkeys under modulations of the glutamatergic and cholinergic systems using [ 15 O] H 2 O and positron emission tomography (PET). Under a saline condition, vibrotactile stimulation elicited a significant increase in the rCBF response in the contralateral somatosensory cortex. The systemic administration of scopolamine, a muscarinic cholinergic receptor antagonist, resulted in the dose-dependent reduction of the rCBF response to the stimulation. The rCBF response abolished by scopolamine was recovered by the administration of physostigmine, a cholinesterase inhibitor in a dose-dependent manner. In addition, d-cycloserine, a partial agonist at the glycine site coupled to N-methyl- d-aspartate (NMDA) receptors, also restored the scopolamine-abolished rCBF response. The regional cerebral metabolic rate of glucose (rCMRglc) response, measured with [ 18 F] -2-fluoro-2-deoxy- d-glucose, was not affected by the administration of scopolamine, physostigmine and/or d-cycloserine. The systemic administration of (+)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), an antagonist of the glycine modulatory site on the NMDA receptors, induced the dose-dependent suppression of the rCBF response to the stimulation. The rCBF response abolished by HA-966 was restored by d-cycloserine, but not by physostigmine. The rCMRglc response was partially but significantly reduced by the administration of HA-966, and its reduction was restored by d-cycloserine, but not by physostigmine. These findings provided pharmacological evidence for an interaction between cholinergic and glutamatergic neuronal systems, the latter of which mediates the former by downstream regulation, in the functional rCBF response to somatosensory stimulation.