Effects of Cholinergic Compounds in Methamphetamine‐discrimination Studies

Abstract

Accumulating evidence suggests that acetylcholine nicotinic mechanisms may contribute to the abuse‐related effects of methamphetamine (MA). In the present study, effects of indirect dopamine (DA) agonists, (d‐amphetamine, L‐MA, cocaine, GBR 12909, methylphenidate), full [nicotine (NIC), anabasine (ANA), (+)‐epibatadine, (−)‐epibatadine, isoarecolone] and partial [varenicline (VAR)] nicotinic agonists, and other cholinergic compounds (atropine, scopolamine, rivastigmine, donepezil) were examined in rats that discriminated 0.3 mg/kg i.p. MA from saline. All indirect DA agonists fully substituted for MA in a dose‐related manner. Among cholinergic agonists, NIC fully substituted for MA in a dose‐dependent manner, whereas other nicotinic agonists produced partial MA‐like responding. Other cholinergic compounds, failed to substitute for MA. In additional experiments, nicotinic agonists were examined in squirrel monkeys that discriminated 0.1 mg/kg i.m. MA from saline. NIC fully substituted for MA, whereas ANA and VAR produced partial MA‐lever responding. These results are consistent with the idea that nicotinic activity plays a role in the abuse‐related effects of MA, and may provide a mechanism for anti‐stimulant medication development (supported by ARRA‐NIH‐NIDA DA026548‐01A1).