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Inhibitory effects of dopamine and methylenedioxymethamphetamine (MDMA) on glutamate-evoked firing of nucleus accumbens and caudate/putamen cells are enhanced following cocaine self-administration.

S R White, G C Harris, K M Imel, M J Wheaton

Brain Research May 1, 1995 DOI: 10.1016/0006-8993(95)00309-e (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Population Rats self-administering cocaine, compared with control rats
Interventions Cocaine Dopamine Methylenedioxymethamphetamine (MDMA) Glutamate
Duration 15 days of 3-hour self-administration sessions; testing 1-11 days after last exposure
Topics MDMA
Keywords Brain Caudate nucleus Putamen Nucleus accumbens Neurons Animals Rats, sprague-dawley N-methyl-3,4-methylenedioxyamphetamine Cocaine Glutamic acid Dopamine uptake inhibitors Self administration Iontophoresis Dose-response relationship, drug Male
Key findings Dopamine inhibited glutamate-evoked firing in the nucleus accumbens and caudate/putamen of both cocaine-exposed and control rats, but this inhibition was significantly greater after repeated cocaine self-administration, in both early (1-3 day) and later (9-11 day) abstinence. Nucleus accumbens cells were also sensitized to MDMA's inhibitory effects. The authors conclude that long-term neuroadaptations occur in these regions after repeated self-administered cocaine.

Abstract

Rats were allowed to self-administer cocaine during a 3-h session for 15 days. One to 11 days after the last cocaine exposure, rats were anesthetized with urethane and effects of microiontophoretically-applied dopamine on glutamate-evoked firing of neurons in the nucleus accumbens and in the caudate/putamen were tested. Dopamine produced a dose-dependent inhibition of glutamate-evoked firing in both the nucleus accumbens and the caudate/putamen of rats that had been repeatedly exposed to self-administered cocaine and in control rats. However, the DA-induced inhibition was significantly greater in the group that had self-administered cocaine. The cocaine self-administration group was significantly sensitized to the inhibitory effects of dopamine in both early (1-3 day) and later (9-11 days) periods of cocaine abstinence. Following cessation of repeated cocaine self-administration sessions, nucleus accumbens cells were also sensitized to the inhibitory effects of methylenedioxymethamphetamine (MDMA), a drug that increases extracellular levels of DA and serotonin in the nucleus accumbens. This sensitization to DA- and MDMA-induced inhibition in the nucleus accumbens and in the striatum indicates that long-term neuroadaptations occur in these regions of the nervous system following repeated exposure to self-administered cocaine.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

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