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

Date

2021-07-30

Advisors

Journal Title

Journal ISSN

ISSN

Volume Title

Publisher

Elsevier

Type

Article

Peer reviewed

Yes

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 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 longlasting consequences on midbrain dopamine neurons, via glutamatergic-dependent mechanisms.

Description

preclinical study on the psychostimulant and ADHD drug methylphenidate The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.

Keywords

Neuropsychopharmacology, electrophysiology, dopamine neurons, methylphenidate, glutamate, attention deficit and hyperactivity disorder (ADHD)

Citation

Di Miceli, M., Omoloye, A., Gronier, B. (2021) Characterisation of methylphenidate-induced excitation in midbrain dopamine neurons, an electrophysiological study in the rat brain. Progress in Neuropsychopharmacology & Biological Psychiatry, 112,110406

Rights

Research Institute

Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)