Behavioral sensitivity to amphetamine or scopolamine after acute administration of nicotine in the rat

Earlier experiments have revealed that a single pretreatment of the rat with chlorphenvinphos (CVP) at a subtoxic dose (1.0 mg/kg, about 1/10 of DL50) makes the animal hyposensitive to the locomotor stimulating effect of amphetamine (AMPH) or scopolamine (SCOP) given three weeks postexposure. Such a hyposensitivity did not develop after a single or multiple (at short intervals) dosing with oxotremorine (OXO), a direct muscarinic agonist, which suggests that it was not mediated by muscarinic receptors. The purpose of the present experiment was to find out whether activation of nicotinic receptors could induce behavioral hyposensitivity to AMPH.

Male adult Wistar rats were pretreated once with 0.00, 0.5 or 1.0 mg/kg of nicotine (NIC), a nicotinic agonist, and challenged 15 days later with 1.0 mg/kg of AMPH or 0.75 mg/kg of SCOP. The pre- and postdrug open-field behavior of the rats was measured using a computerized set of activity meters.

Pretreatment with NIC, like pretreatment with OXO, did not make the animals hyposensitive to AMPH or SCOP. In a preliminary experiment we have also found that rats do not develop hyposensitivity to AMPH and SCOP after pretreatment with physostigmine, a reversible anticholinesterase and a direct nicotinic and possibly muscarinic agonist.

The results suggest that a transient overstimulation of the cholinergic system cannot be the cause or a sufficient condition for the development of the CVP-induced diminution of sensitivity to AMPH and SCOP.