title: Interactions between modafinil and cocaine during the induction of conditioned place preference and locomotor sensitization in mice: implications for addiction.
abstract: Modafinil is a wake-promoting drug effective at enhancing alertness and attention with a variety of approved and off-label applications. The mechanism of modafinil is not well understood but initial studies indicated a limited abuse potential. A number of recent publications, however, have shown that modafinil can be rewarding under certain conditions. The present study assessed the reinforcing properties of modafinil using conditioned place preference and locomotor sensitization in mice. Experiment 1 examined a high dose of modafinil (75 mg/kg) as well as its interactions with cocaine (15 mg/kg). Cocaine alone and modafinil co-administered with cocaine induced sensitization of locomotor activity; modafinil alone showed little or no locomotor sensitization. Animals given modafinil alone, cocaine alone, and modafinil plus cocaine exhibited a strong and roughly equivalent place preference. When tested for sensitization using a low challenge dose of modafinil, cross-sensitization was observed in all cocaine-pretreated mice. Experiment 2 examined a low dose of modafinil that is similar to the dose administered to humans and has been shown to produce cognitive enhancements in mice. Low dose modafinil (0.75 mg/kg) did not produce conditioned place preference or locomotor sensitization. Together, these results suggest that modafinil has the potential to produce reward, particularly in cocaine addicts, and should be used with caution. However, the typical low dose administered likely moderates these effects and may account for lack of addiction seen in humans.
authors.affiliation: Molecular Cognition Laboratory, Department of Psychology, University of California, San Diego, La Jolla, CA 92093-0109, United States. tshuman@ucla.edu
authors.forename: Tristan
authors.initials: T
authors.lastname: Shuman
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Cai
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Sage
authors.forename: Stephan G
authors.initials: SG
authors.lastname: Anagnostaras
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D059333:Central Nervous System Sensitization / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000077408:Modafinil; D015999:Multivariate Analysis; D012201:Reward; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D000077408:Modafinil