A novel nicotinic-cholinergic role in behavioral sensitization to amphetamine-induced stereotypy in mice

Cholinergic antagonists were used to investigate the role of the cholinergic system in amphetamine- and cocaine-induced behavioral sensitization to stereotypy in mice. Systemically, mecamylamine (1 mg/kg) and dihydro-beta-erythroidine (2 mg/kg) - nicotinic antagonists - and atropine (2 mg/kg) - a muscarinic antagonist - were ineffective against psychostimulant-induced stereotypy in naive animals. The nicotinic antagonists, however, blocked both the induction and expression of sensitization to amphetamine; in contrast, atropine was ineffective. All three drugs were ineffective against either the induction or expression of cocaine sensitization. Intrastriatally, the nicotinic antagonists blocked induction but not expression of amphetamine-induced sensitization. The results suggest that the nicotinic system participates in sensitization induced by amphetamine but not cocaine; that the nicotinic component of the amphetamine response in sensitized animals is novel as compared to the response in naive animals; and that the striatum is a locus for the nicotinic involvement in induction but not expression. The data add support to the inference that behavioral sensitization represents not only a quantitative but a qualitative change in response to amphetamine.