Nicotine reduces the binding of [3H]MK-801 to brain membranes, but not via the stimulation of high-affinity nicotinic receptors.

Nicotine (10 and 100 microM) inhibited [3H]MK-801 binding to rat cerebral cortical membranes and this effect was not blocked by dihydro-beta-erythroidine, (+)-tubocurarine or mecamylamine. Cytisine, muscarine mecamylamine and (+)-tubocurarine also inhibited [3H]MK-801 binding. Neither raising the MK-801 concentration, nor the addition of n-methyl-D-aspartate (NMDA) receptor agonists altered the effects of nicotine. Hence this response is not mediated via high-affinity nicotinic receptor stimulation, competition for MK-801 binding sites or require NMDA receptor activation.