Drug seeking in response to a priming injection of MDMA in rats: relationship to initial sensitivity to self-administered MDMA and dorsal striatal dopamine.

In laboratory animals, exposure to priming injections of 3,4-methylenedioxymethamphetamine (MDMA) produced drug seeking following extinction of MDMA self-administration. This study aimed to evaluate whether the magnitude of drug seeking was related to latency to acquisition of MDMA self-administration and increases in striatal dopamine, as measured by in-vivo microdialysis. Rats were given daily access to MDMA self-administration until they earned a total of 240 infusions (total intake of 165 mg/kg MDMA). Twelve of the 20 rats acquired self-administration within the temporal limits of the study and the latency to meet the criterion ranged from 9 d to 37 d. An experimenter-administered injection of MDMA (10.0 mg/kg i.p.) produced drug seeking in these rats, and the number of responses was significantly higher than responses produced by rats that failed to meet the criterion or by yoked control rats that received the drug passively. For rats that met the criterion, drug seeking was negatively correlated with the number of days to self-administer the criterion number of MDMA infusions and positively correlated with MDMA-produced dopamine in the dorsal striatum. Importantly, MDMA-produced dopamine overflow was greater for the rats that met the criterion. These findings suggest that drug seeking is influenced by initial sensitivity to the reinforcing effects of MDMA and to drug-produced increases in striatal dopamine.