Dextromethorphan diminishes methamphetamine's effects

Dextromethorphan is a cough suppressant found in Robitussin-DM and Mucinex-DM and binds to a number of sites in the brain related to drug abuse and dependence, including opioid receptors, sigma receptors, glutamate receptors and neurotransmitter transporters.  Pao-Pao Yang and colleagues recently published a research article in the journal Synapse indicating that dextromethorphan could be a treatment for craving for methamphetamine craving.  In their experiment, dextromethorphan microinjection into brain regions associated with drug abuse and dependence (the nucleus accumbens and ventral tegmental area) decreased methamphetamine-seeking during a methamphetamine withdrawal period.

Reference - Yang PP et al (2012) Post-treatment of dextromethorphan on methamphetamine-induced drug-seeking and behavioral sensitization in rats. Synapse

Donepezil (Aricept) blocks cocaine's, but not methamphetamine's, effects

Donepezil is used to manage the early symptoms of Alzheimer's Disease and is available as the Aricept preparation.  It is a cholinesterase inhibitor, and increases acetylcholine levels in brain.  Our lab group recently reviewed a paper by Takamatsu and colleages on donepezil's efficacy to block the conditioned reinforcing (place preference) and locomotor activating properties of cocaine and methamphetamine in mice.  While it diminished the effects of cocaine, it was ineffective to alter methamphetamine's effects in this study.  Considering the efficacy of other cholinergic ligands (e.g., lobeline) to alter methamphetamine's effects, these findings were surprising to us.

Reference - Takamatus Y. et al. (2006) Differential effects of donepezil on methamphetamine and cocaine depedencies.  Ann NY Acad Sci 1074: 418

Methamphetamine place preference

Our laboratory at the University of Missouri is working to develop a place preference assay to evaluate the conditioned-rewarding properties of methamphetamine in mice.  We were able to develop a cocaine place preference procedure, but have been struggling with methamphetamine.  Any suggestions would be appreciated!