Departmental Affiliation and City, State, Zip for All Authors

College of Arts and Sciences, Atlanta, Georgia, 30322; Texas College of Osteopathic Medicine, Fort Worth, Texas, 76107; Department of Pharmacology and Neuroscience, Fort Worth, 76107; Department of Pharmacology and Neuroscience, Fort Worth, 76107

Scientific Abstract

Pro-oxidizing redox signals are thought to play a significant role in memory formation. The production of reactive oxygen species (ROS) as a consequence of cocaine use may, therefore, facilitate the formation of drug-associated memories. We hypothesized that a pharmacological treatment using N,N′-dimethylthiourea (DMTU), a hydroxyl radical scavenger permeable to the blood-brain barrier, could attenuate the expression of cocaine-associated drug memory. The conditioned place preference (CPP) paradigm, an animal model of drug-associated memories based on Pavlovian conditioning, was used to test the hypothesis. Four doses of DMTU (5, 10, 50 or 100 mg/kg) were tested after CPP had been established using 15 mg/kg of cocaine. The cocaine CPP training resulted in 3 distinct phenotypes that have been observed previously: (i) high cocaine seekers, (ii) low seekers, and (iii) cocaine avoiders. DMTU significantly attenuated cocaine-induced CPP in high seekers after 10 mg/kg. DMTU dose of 100 mg/kg attenuated cocaine-induced CPP in avoiders. The results are consistent with the hypothesis that redox signals are involved in drug-associated memory expression and that DMTU can block the memory of an environmental stimulus cue associated with drug use. Behavioral depression at higher doses of DMTU such as 50 mg/kg and 100 mg/kg could account for the better results after 10 mg/kg. These results suggest that DMTU could be used to treat addiction and prevent relapse.

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THE EFFECT OF N,N′-DIMETHYLTHIOUREA ON EXPRESSION OF COCAINE-INDUCED CONDITIONED PLACE PREFERENCE

Pro-oxidizing redox signals are thought to play a significant role in memory formation. The production of reactive oxygen species (ROS) as a consequence of cocaine use may, therefore, facilitate the formation of drug-associated memories. We hypothesized that a pharmacological treatment using N,N′-dimethylthiourea (DMTU), a hydroxyl radical scavenger permeable to the blood-brain barrier, could attenuate the expression of cocaine-associated drug memory. The conditioned place preference (CPP) paradigm, an animal model of drug-associated memories based on Pavlovian conditioning, was used to test the hypothesis. Four doses of DMTU (5, 10, 50 or 100 mg/kg) were tested after CPP had been established using 15 mg/kg of cocaine. The cocaine CPP training resulted in 3 distinct phenotypes that have been observed previously: (i) high cocaine seekers, (ii) low seekers, and (iii) cocaine avoiders. DMTU significantly attenuated cocaine-induced CPP in high seekers after 10 mg/kg. DMTU dose of 100 mg/kg attenuated cocaine-induced CPP in avoiders. The results are consistent with the hypothesis that redox signals are involved in drug-associated memory expression and that DMTU can block the memory of an environmental stimulus cue associated with drug use. Behavioral depression at higher doses of DMTU such as 50 mg/kg and 100 mg/kg could account for the better results after 10 mg/kg. These results suggest that DMTU could be used to treat addiction and prevent relapse.

Manuscript Number

1046