TY - JOUR
T1 - Modafinil potentiates cocaine self-administration by a dopamine-independent mechanism
T2 - possible involvement of gap junctions
AU - Mereu, Maddalena
AU - Hiranita, Takato
AU - Jordan, Chloe J.
AU - Chun, Lauren E.
AU - Lopez, Jessica P.
AU - Coggiano, Mark A.
AU - Quarterman, Juliana C.
AU - Bi, Guo Hua
AU - Keighron, Jacqueline D.
AU - Xi, Zheng Xiong
AU - Newman, Amy Hauck
AU - Katz, Jonathan L.
AU - Tanda, Gianluigi
N1 - Publisher Copyright:
© 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41386-020-0680-5
DO - 10.1038/s41386-020-0680-5
M3 - Article
C2 - 32340023
AN - SCOPUS:85084131810
SN - 0893-133X
VL - 45
SP - 1518
EP - 1526
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 9
ER -