Effects of Physostigmine on the Startle in Guinea Pigs: Two Mechanisms Involved

The effects of the acetylcholinesterase inhibitor physostigmine (PHY) on the auditory startle reflex in guinea pigs were studied. The dose–response curve of PHY appeared bell shaped, with a maximum effect dose of 0.3 mg/kg. In addition, PHY altered the shape of the startle response. The muscarinic antagonist scopolamine (SCO) increased the startle at PHY doses above 0.3 mg/kg without affecting the PHY-induced shape of the response. The decreasing part of the startle due to PHY could be mimicked by the cholinesterase inhibitor soman in combination with 0.3 mg/kg PHY. It appeared that the decreasing part of the dose–response curve at higher dose levels is caused by the cholinesterase inhibitory action of PHY and, in view of the SCO effect, is mediated by muscarinergic receptors. The increasing part of the curve is probably caused by an agonistic action of PHY on neuronal nicotinergic receptors, because the antagonist mecamylamine (20 mg/kg) antagonized the effects of 0.3 mg/kg PHY both on the deflection and shape of the startle.