Characterisation of methylphenidate-induced excitation in midbrain dopamine neurons, an electrophysiological study in the rat brain.
Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2021-07-01; : 110406
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Di Miceli M(1), Omoloye A(2), Gronier B(3).
(1)Pharmacology and Neuroscience Research Group, Leicester School of Pharmacy, De
Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom; Laboratoire
NutriNeuro, UMR INRAE 1286, Université de Bordeaux, Bordeaux, France.
(2)Pharmacology and Neuroscience Research Group, Leicester School of Pharmacy, De
Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom.
(3)Pharmacology and Neuroscience Research Group, Leicester School of Pharmacy, De
Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom. Electronic
Methylphenidate (MPH) is a drug routinely used for patients with attention
deficit and hyperactivity disorder (ADHD). Concerns arise about psychostimulant
use, with dramatic increases in prescriptions. Besides, antipsychotic drugs are
often administered in combination with MPH. In this study, we examine the
consequences of MPH exposure in combination with dopamine D2 receptor antagonism
(eticlopride) on midbrain dopaminergic neurons in anaesthetised rodents, using in
vivo extracellular single-cell electrophysiology. As expected, we show that
methylphenidate (2 mg/kg, i.v.) decreases the firing and bursting activities of
ventral tegmental area (VTA) dopamine neurons, an effect that is reversed with
eticlopride (0.2 mg/kg, i.v.). However, using such a paradigm, we observed higher
firing and bursting activities than under baseline conditions. Furthermore, we
demonstrate that such an effect is dependent on dual alpha-1 and dopamine D1
receptors, as well as glutamatergic transmission, through glutamate
N-Methyl-D-aspartate (NMDA) receptor activation. Chronic MPH treatment during
adolescence greatly dampens MPH-induced excitatory effects measured at adulthood.
To conclude, we demonstrated here that a combination of methylphenidate and a
dopamine D2 receptor antagonist produced long-lasting consequences on midbrain
dopamine neurons, via glutamatergic-dependent mechanisms.
Copyright © 2021. Published by Elsevier Inc.