Abstract
Studies on the abuse potential of modafinil, a psychostimulant-like drug used to treat narcolepsy, are still controversial. While some studies claim no potential for abuse, increasing evidence suggests that modafinil induces abuse-related effects, including rapid-onset behavioral sensitization (i.e., a type of sensitization that develops within hours from the drug priming administration). The rapid-onset sensitization paradigm is a valuable tool to study the neuroplastic changes that occur quickly after drug administration, and shares neuroadaptations with drug abuse in humans. However, the mechanisms involved in the rapid-onset behavioral sensitization induced by modafinil are uncertain. Our aim was to investigate the possible involvement of dopamine D1 and D2 receptors on acute modafinil-induced hyperlocomotion and on the induction and expression of rapid-onset behavioral sensitization induced by modafinil in male Swiss mice. Treatment with the D1 receptor antagonist SCH 23390 or the D2 receptor antagonist sulpiride attenuated the acute modafinil-induced hyperlocomotion in a dose-dependent manner. Pretreatment with either antagonist before the priming injection of modafinil prevented the development of sensitization in response to a modafinil challenge 4 h later. However, only SCH 23390 decreased the expression of modafinil-induced rapid-onset behavioral sensitization. Taken together, the present findings provide evidence of the participation of D1 and D2 receptors on the development of rapid-onset behavioral sensitization to modafinil, and point to a prominent role of D1 receptors on the expression of this phenomenon.
Highlights
IntroductionModafinil (diphenyl-methyl sulphonyl-2-acetamide) is a wakepromoting drug with psychostimulant properties that has been approved for the treatment of excessive daytime sleepiness in narcolepsy, obstructive sleep apnea and shift workers sleep disorder (Minzenberg and Carter, 2008)
Modafinil is a wakepromoting drug with psychostimulant properties that has been approved for the treatment of excessive daytime sleepiness in narcolepsy, obstructive sleep apnea and shift workers sleep disorder (Minzenberg and Carter, 2008)
Animals treated with 64 mg/kg modafinil alone (Mod) showed a significant increase in locomotor activity when compared to animals treated with vehicle (Veh), demonstrating the locomotor stimulant effect induced by this dose of modafinil
Summary
Modafinil (diphenyl-methyl sulphonyl-2-acetamide) is a wakepromoting drug with psychostimulant properties that has been approved for the treatment of excessive daytime sleepiness in narcolepsy, obstructive sleep apnea and shift workers sleep disorder (Minzenberg and Carter, 2008). Modafinil alone seems to exert rewarding properties, as it produces conditioned place preference and induces robust behavioral sensitization after single- and repeated-injection treatments in mice (Paterson et al, 2010; Wuo-Silva et al, 2011; Shuman et al, 2012). Modafinil has been shown to induce rapid-onset behavioral sensitization in mice using a paradigm in which sensitization is developed when a challenge drug injection is administered only a few hours after a priming injection of a high dose of the same drug (Wuo-Silva et al, 2016)
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