Effects of muscarinic and adrenergic agonism on auditory P300 in the macaque

Homologs of human endogenous evoked potentials are known in several species of nonhuman primates, but the neurotransmitter substrates of these potentials remain uncertain. In particular, the role of central cholinergic and adrenergic systems is not yet clearly defined. We recorded cognitive evoked potentials from the scalp in four adult bonnet macaque monkeys during a passive version of the auditory oddball paradigm with unique novel stimuli under saline control conditions. In two subjects each, cognitive evoked potentials were also recorded following intramuscular administration of the m1 muscarinic agonist AF102B or of the alpha-2A noradrenergic agonist guanfacine. On saline, large positivities resembling the human P300 were recorded over midline sites in response to rare or novel auditory stimuli in all four monkeys. The amplitude of these positivities was sensitive to the delivery of fruit-juice reward in association with rare stimuli in three monkeys tested. At cognition-enhancing doses, AF102B enlarged the amplitude of P300-like positivities in both monkeys tested; guanfacine enlarged the amplitude of P300-like positivities in one of two monkeys tested. These results add to existing evidence of human-like endogenous late positivities in monkeys that are influenced by the cholinergic and adrenergic systems, and suggest a possible role of m1 muscarinic and alpha-2A noradrenergic receptor subtypes.