The Effect of Methadone Administration on Cocaine-Conditioned Hyperactivity and Sensitization in Mice



Journal Title

Journal ISSN

Volume Title



Substance abuse disorder is characterized by compulsive drug-seeking behavior regardless of negative consequences. Methadone, a synthetic opioid, has been used as an effective treatment to aid rehabilitating patients to resist opioid relapse. One factor complicating opioid recovery is the frequent and concurrent use of cocaine during medication-assisted treatment (MAT) programs. Both methadone and cocaine act on the reward pathway of the brain to produce distinct and complementary changes in drug-associated behaviors and memories. There are open questions about the effects of opioid treatment drugs on cocaine-associated behavior and memory. To that end, this study investigated the effect of chronic and acute methadone administration on cocaine-conditioned hyperactivity and sensitization in mice. In the first experiment, mice received daily methadone injections before undergoing cocaine-conditioning. After conditioning, mice were tested for locomotor sensitization (a cocaine-associated behavior), conditioned hyperactivity (cocaine-associated memory) and reinstatement (reflecting susceptibility for relapse). For the second experiment, mice received a single acute dose of methadone before undergoing cocaine conditioning and testing for locomotor sensitization, conditioned hyperactivity and reinstatement. Results indicated that chronic methadone does not affect the rate of cocaine sensitization, conditioned hyperactivity, or reinstatement. However, a trend suggests that chronic methadone may affect the magnitude of the locomotor activating effect of cocaine. Similarly, acute methadone was found to have no effect on cocaine sensitization or conditioned hyperactivity, but an interaction revealed that acute methadone enhanced cocaine reinstatement. These results could have important implications for the treatment of patients who continue to use cocaine while participating in MAT programs.



cocaine, methadone, polydrug use, methadone maintenance, sensitization, substance abuse disorder, drug addiction, memory, reinstatement, opioid, psychostimulant, medication-assisted treatment, conditioned hyperactivity, cocaine-associated behavior, chronic methadone, acute methadone