Individual differences are critical in determining modafinil-induced behavioral sensitization and cross-sensitization with methamphetamine in mice

• Published in: Behavioural brain research 2012-08, Vol.233 (2), p.367-374
• Main Authors: Soeiro, Aline da Costa, Moreira, Karin Di Monteiro, Abrahao, Karina Possa, Quadros, Isabel Marian Hartmann, Oliveira, Maria Gabriela Menezes
• Format: Article
• Language: English
• Subjects: Amphetamines; Analysis of Variance; Animals; Association Learning - drug effects; Avoidance Learning - drug effects; Behavior, Animal - drug effects; Benzhydryl Compounds - pharmacology; Central Nervous System Stimulants - pharmacology; Conditioning (Psychology) - drug effects; Dose-Response Relationship, Drug; Drugs of abuse; Exploratory Behavior - drug effects; Fear - drug effects; Individual variability; Individuality; Locomotor activity; Locomotor sensitization; Male; Methamphetamine - pharmacology; Mice; Motor Activity - drug effects; Time Factors
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2012.05.023

► Behavioral sensitization to modafinil and methamphetamine was assessed in mice. ► There are important individual differences in sensitization to both drugs. ► Modafinil sensitization was clearly expressed only in a subgroup of mice. ► Expression of modafinil, but not methamphetamine, sensitization was context-dependent. ► Modafinil–methamphetamine cross-sensitization only occurred in a subgroup of mice. Modafinil is a non-amphetaminic psychostimulant used therapeutically for sleep and psychiatric disorders. However, some studies indicate that modafinil can have addictive properties. The present study examined whether modafinil can produce behavioral sensitization in mice, an experience and drug-dependent behavioral adaptation, and if individual differences play a role in this process. We further tested context-related factors and cross-sensitization between modafinil and methamphetamine. Important individual differences in the behavioral sensitization of Swiss Albino mice were observed after repeated administration of 50mg/kg modafinil (Experiment 1), or 1mg/kg methamphetamine (Experiment 2). Only mice classified as sensitized subgroup developed clear behavioral sensitization to the drugs. After a withdrawal period, mice received challenges of modafinil (Experiment 1), or methamphetamine (Experiment 2) and locomotor activity was evaluated in the activity cages (previous context) and in the open field arena (new context) in order to evaluate the context dependency of behavioral sensitization. The expression of sensitization to modafinil, but not to methamphetamine, was affected by contextual testing conditions, since modafinil-sensitized mice only expressed sensitization in the activity cage, but not in the open field. Subsequently, locomotor cross-sensitization between methamphetamine and modafinil was assessed by challenging modafinil-pretreated mice with 1mg/kg methamphetamine (Experiment 1), and methamphetamine-pretreated mice with 50mg/kg modafinil (Experiment 2). We observed a symmetrical cross-sensitization between the drugs only in those mice that were classified as sensitized subgroup. Our findings indicate that repeated exposure to modafinil induces behavioral sensitization only in some animals by similar neurobiological, but not contextual, mechanisms to those of methamphetamine.