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.

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

“…This may be related to the higher nicotine dose used in the P-rats (60 mg/kg/infusion) than that used in the Long-Evans rats (30 mg/kg/infusion). We also note that (±)-MOD produces conditioned place preference (Nguyen et al, 2011;Shuman et al, 2012). However, in this study, R-MOD substitution failed to sustain self-administration in rats previously self-administering nicotine.…”

Sensitized nucleus accumbens dopamine terminal responses to methylphenidate and dopamine transporter releasers after intermittent-access self-administration

“…Although it is not at novel concept that exposure to one stimulant may increase the abuse potential for other stimulants (Shuman et al, 2012; Rosine et al, 2009; Valvassori et al, 2007; Tronci et al, 2006; Yang et al, 2003), this paper is particularly relevant when considering previous data on cross sensitization of stimulants. While many groups have previously shown that stimulants do, indeed, produce cross sensitization and cross-tolerance (Shuman et al, 2012; Rosine et al, 2009; Valvassori et al, 2007; Tronci et al, 2006; Yang et al, 2003; Ferris et al, 2012, 2013a; Calipari et al, 2013c), here we expand and clarify this idea.…”

Psychostimulants and Cognition: A Continuum of Behavioral and Cognitive Activation

“…was not reinforcing when administered alone (Deroche-Gamonet et al, 2002); however, we have recently found that modafinil (75 mg/kg i.p.) alone can produce a conditioned place preference (Shuman et al, 2012), indicating that modafinil is at least a weak reinforcer. Indeed, administration of modafinil (800 mg, roughly 10 mg/kg p.o.)…”