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

Autor: Raphael Wuo-Silva, Daniela F. Fukushiro-Lopes, Bruno P. Fialho, André W. Hollais, Renan Santos-Baldaia, Eduardo A. V. Marinho, Elisa Mári-Kawamoto, Thaís S. Yokoyama, Leonardo B. Lopes-Silva, Laís F. Berro, Roberto Frussa-Filho, Beatriz M. Longo
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 10 (2019)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2019.00211
Popis: 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.
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