Differential effects of donepezil on methamphetamine and cocaine dependencies

Ann N Y Acad Sci. 2006 Aug;1074:418-26. doi: 10.1196/annals.1369.042.


Donepezil, a choline esterase inhibitor, has been widely used as a medicine for Alzheimer's disease. Recently, a study showed that donepezil inhibited addictive behaviors induced by cocaine, including cocaine-conditioned place preference (CPP) and locomotor sensitization to cocaine. In the present study, we investigated the effects of donepezil on methamphetamine (METH)-induced behavioral changes in mice. In counterbalanced CPP tests, the intraperitoneal (i.p.) administration of 3 mg/kg donepezil prior to 2 mg/kg METH i.p. failed to inhibit METH CPP, whereas pretreatment with 3 mg/kg donepezil abolished the CPP for cocaine (10 mg/kg, i.p.). Similarly, in locomotor sensitization experiments, i.p. administration of 1 mg/kg donepezil prior to 2 mg/kg METH i.p. failed to inhibit locomotor sensitivity to METH, whereas pretreatment with 1 mg/kg donepezil significantly inhibited locomotor sensitivity to cocaine (10 mg/kg, i.p.). These results suggest that donepezil may be a useful tool for treating cocaine dependence but not for treating METH dependence. The differences in the donepezil effects on addictive behaviors induced by METH and cocaine might be due to differences in the involvement of acetylcholine in the mechanisms of METH and cocaine dependencies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine-Related Disorders / drug therapy
  • Animals
  • Behavior, Animal / drug effects
  • Cocaine-Related Disorders / drug therapy
  • Conditioning, Psychological
  • Donepezil
  • Indans / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Piperidines / pharmacology*


  • Indans
  • Piperidines
  • Donepezil