Characterisation of methylphenidate-induced excitation in midbrain dopamine neurons, an electrophysiological study in the rat brain

Di Miceli, Mathieu ORCID: https://orcid.org/0000-0003-3713-0370, Omoloye, A. and Gronier, B. (2021) Characterisation of methylphenidate-induced excitation in midbrain dopamine neurons, an electrophysiological study in the rat brain. Progress in neuro-psychopharmacology & biological psychiatry, 112. p. 110406. ISSN 0278-5846

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Abstract

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 D 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 D 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 D receptor antagonist produced long-lasting consequences on midbrain dopamine neurons, via glutamatergic-dependent mechanisms.

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