Repeated restraint stress potentiates methylphenidate and modafinil-induced behavioral sensitization in rats

Stress increases the susceptibility of drug abuse and drugs of abuse impair behavioral tolerance. It has been shown that stress exposure enhances the sensitivity to the reinforcing properties of drugs, augments locomotor sensitization effects of drugs of abuse and impairs behavioral tolerance. Previously, it has been shown that long-term administration of psychostimulants (Methylphenidate and Modafinil) induced locomotor sensitization effect that was more pronounced after 13 days of drug administration and was greater at high dose. The present study is designed to investigate the relationship between restraint stress and psychostimulants (Methylphenidate and Modafinil) that induced sensitization. Methylphenidate (10 mg/kg/day twice a day), modafinil (75 mg/kg/day once daily), and saline (0.9% NaCl; 1 ml/kg/day) were administered orally to treated and control animals. Rats were exposed to immobilization stress for 30 days (until locomotor sensitization produced) to monitor any change in drug-induced behavioral sensitization. The motor activity was compared daily by using familiar environment of home cage and weekly by novel environment of open field. The results show that the methylphenidate and modafinil-induced locomotor sensitization is enhanced and impaired behavioral tolerance in repeated restrained rats. It shows that the psychostimulants like methylphenidate and modafinil produce greater locomotor sensitization in stressful environment, suggesting addictive effects of stress and psychostimulants (methylphenidate/modafinil) on dopaminergic neurotransmission. These finding may be helpful to develop potential pharmacotherapies for the patients with co-occurring depression and substance abuse/dependence disorder.