Journal Article

Participation of Dopamine D1 and D2 Receptors in the Rapid-Onset Behavioral Sensitization to Modafinil

Longo, Beatriz M., Fukushiro-Lopes, Daniela F., Frussa-Filho, Roberto, Hollais, André W., Lopes-Silva, Leonardo B., Marinho, Eduardo A. V., Santos-Baldaia, Renan, Mári-Kawamoto, Elisa, Wuo-Silva, Raphael, Fialho, Bruno P., Berro, Laís F., Yokoyama, Thaís S.

2019

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Cocaine / Dopamine / Dopamine D1 receptors / Dopamine D2 receptors / Drug abuse / Drug dosages / Laboratory animals / mice / Modafinil / Pharmacology / rapid-onset behavioral sensitization / SCH 23390 / Sleep disorders / Sulpiride