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

Author(s):Show less -

Wuo-Silva, Raphael ^{[1, 2]} ; Fukushiro-Lopes, Daniela F. ^[1] ; Fialho, Bruno P. ^[2] ; Hollais, Andre W. ^[2] ; Santos-Baldaia, Renan ^[2] ; Marinho, Eduardo A. V. ^[3] ; Mari-Kawamoto, Elisa ^[1] ; Yokoyama, Thais S. ^[1] ; Lopes-Silva, Leonardo B. ^[1] ; Berro, Lais F. ^[4] ; Frussa-Filho, Roberto ^[1] ; Longo, Beatriz M. ^[2]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Pharmacol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Physiol, Lab Neurophysiol, Sao Paulo - Brazil

^[3] Univ Estadual Santa Cruz, Dept Hlth Sci, Ilheus - Brazil

^[4] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 - USA

• Document type: Journal article
• Source: FRONTIERS IN PHARMACOLOGY; v. 10, MAR 11 2019.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 17/12412-2 - Degenerative and regenerative processes in Alzheimer's Disease: from cell culture to cell therapy
• Grantee: Beatriz de Oliveira Monteiro
• Support Opportunities: Regular Research Grants