Modafinil potentiates cocaine self-administration by a dopamine-independent mechanism: possible involvement of gap junctions

Maddalena Mereu, Takato Hiranita, Chloe J. Jordan, Lauren E. Chun, Jessica P. Lopez, Mark A. Coggiano, Juliana C. Quarterman, Guo Hua Bi, Jacqueline D. Keighron, Zheng Xiong Xi, Amy Hauck Newman, Jonathan L. Katz, Gianluigi Tanda

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Modafinil and methylphenidate are medications that inhibit the neuronal reuptake of dopamine, a mechanism shared with cocaine. Their use as “smart drugs” by healthy subjects poses health concerns and requires investigation. We show that methylphenidate, but not modafinil, maintained intravenous self-administration in Sprague-Dawley rats similar to cocaine. Both modafinil and methylphenidate pretreatments potentiated cocaine self-administration. Cocaine, at self-administered doses, stimulated mesolimbic dopamine levels. This effect was potentiated by methylphenidate, but not by modafinil pretreatments, indicating dopamine-dependent actions for methylphenidate, but not modafinil. Modafinil is known to facilitate electrotonic neuronal coupling by actions on gap junctions. Carbenoxolone, a gap junction inhibitor, antagonized modafinil, but not methylphenidate potentiation of cocaine self-administration. Our results indicate that modafinil shares mechanisms with cocaine and methylphenidate but has a unique pharmacological profile that includes facilitation of electrotonic coupling and lower abuse liability, which may be exploited in future therapeutic drug design for cocaine use disorder.

Original languageEnglish (US)
Pages (from-to)1518-1526
Number of pages9
JournalNeuropsychopharmacology
Volume45
Issue number9
DOIs
StatePublished - Aug 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Modafinil potentiates cocaine self-administration by a dopamine-independent mechanism: possible involvement of gap junctions'. Together they form a unique fingerprint.

Cite this