Does that mean you can have your cake and eat it too?? DXM potentiate acute morphine induced DA release while AT THE SAME time attenuates its reinforcing?
- Pretreatment with dextromethorphan (20 mg/kg s.c., 20 min prior) potentiated the effects of acute morphine(~150% of baseline..)
- while attenuating the effects of chronic morphine on nucleus accumbens DA level
DXM has no effect on DA level in the NAcc? I thought it has decent DAT inhibitory activity, or is it NET/SERT selective?Effects of dextromethorphan on dopamine release in the nucleus accumbens: Interactions with morphine. Steinmiller CL1, Maisonneuve IM, Glick SD. Pharmacol Biochem Behav. 2003 Mar;74(4):803-10. http://www.ncbi.nlm.nih.gov/pubmed/12667894
Dextromethorphan has been reported to decrease the self-administration of several drugs of abuse, including morphine, methamphetamine, cocaine, and nicotine. Most drugs of abuse increase extracellular levels of dopamine (DA) in the shell of the nucleus accumbens. The effects of dextromethorphan on DA release in the nucleus accumbens of nai;ve rats and of rats treated acutely and chronically with morphine were studied using in vivo microdialysis. DA dialysate levels were evaluated by high-performance liquid chromatography with electrochemical detection.
Acute morphine (5 mg/kg i.p.) treatment increased the levels of DA in the nucleus accumbens to approximately 175% of basal levels.
Chronic morphine (20 mg/kg i.p. daily for 5 days) increased DA release in the nucleus accumbens to 250% of basal levels.
Acute treatment with dextromethorphan (20 or 30 mg/kg s.c.) alone did not alter nucleus accumbens DA levels.
Pretreatment with dextromethorphan (20 mg/kg s.c., 20 min prior) potentiated the effects of acute morphine, while attenuating the effects of chronic morphine on nucleus accumbens DA levels. These results with dextromethorphan suggest that the mechanism mediating the effects of dextromethorphan on drug self-administration involves modulation of the dopaminergic mesolimbic pathway.