Role of the endocannabinoid system in MDMA intracerebral self‐administration in rats

Rats can learn to self-administer MDMA directly into the brain's ventricles, and the amount they take depends on the dose and on cannabinoid signaling. At most doses, rats pressed a lever more often to receive MDMA, except at the highest dose tested. Adding a synthetic cannabinoid (CP 55,940) to MDMA reduced lever pressing for the drug. Blocking the CB1 cannabinoid receptor with SR 141716A increased MDMA self-administration. These results indicate that the brain's own endocannabinoid system normally restrains MDMA-seeking behavior.

Study at a glance

Abstract

I.c.v. self‐administration of MDMA (0.01–2 μg per infusion), alone and in combination with CP 55,940 (0.4 μg infusion −1 ), was studied on an operant responding procedure. On the basis of individual preference for one of two levers, developed during training, rats were allowed to self‐administer vehicle from the preferred lever and MDMA from the other. Pressings on the MDMA associated‐lever, except for the maximal unit dose, progressively increased. The combination of CP 55,940 with MDMA (1 μg infusion −1 ) reduced the number of drug‐associated lever pressings compared to the single drugs. Pre‐treatment with SR 141716A (0.5 mg kg −1 i.p.), 15 min before each daily session, significantly increased MDMA self‐administration. These findings suggest that MDMA self‐administration is under endogenous tonic control by the endocannabinoid system. British Journal of Pharmacology (2002) 136 , 1089–1092. doi: 10.1038/sj.bjp.0704825