Mecamylamine reverses physostigmine-induced attenuation of scopolamine-induced hyperactivity

It has previously been demonstrated that the muscarinic antagonist scopolamine induces hyperactivity in rodents, which is reversed by physostigmine but not by directly acting agonists such as pilocarpine. This may suggest that non-muscarinic actions of physostigmine may be responsible for its reversal of scopolamine-induced hyperactivity. We have found, in male Wistar rats, whose activity was measured on electromagnetic detector plates, that the central nicotinic receptor antagonist mecamylamine (3 mg/kg) reverses the blockade of scopolamine-induced behavioural activation induced by physostigmine. This suggests that activation of nicotinic receptors can counteract the effects of muscarinic blockade. Interestingly, however, treatment with nicotine does not block scopolamine-induced hyperactivity, suggesting that the exogenous and endogenous ligands may have different receptor or neuronal substrates.