Dissociable rate-dependent effects of oral methylphenidate on impulsivity and D2/3 receptor availability in the striatum

Caprioli, Daniele, Jupp, Bianca, Hong, Young T., Sawiak, Stephen J, Ferrari, Valentina ORCID: https://orcid.org/0000-0003-1895-8906, Wharton, Laura, Williamson, David J., McNabb, Carolyn ORCID: https://orcid.org/0000-0002-6434-5177, Berry, David, Aigbirhio, Franklin I., Robbins, Trevor W., Fryer, Tim D. and Dalley, Jeffrey W. 2015. Dissociable rate-dependent effects of oral methylphenidate on impulsivity and D2/3 receptor availability in the striatum. The Journal of Neuroscience 36 (9) , pp. 3747-3755. 10.1523/jneurosci.3890-14.2015

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Abstract

We have previously shown that impulsivity in rats is linked to decreased dopamine D2/3 receptor availability in the ventral striatum. In the present study, we investigated, using longitudinal positron emission tomography (PET), the effects of orally administered methylphenidate (MPH), a first-line treatment for attention deficit hyperactivity disorder, on D2/3 receptor availability in the dorsal and ventral striatum and related these changes to impulsivity. Rats were screened for impulsive behavior on a five-choice serial reaction time task. After a baseline PET scan with the D2/3 ligand [18F]fallypride, rats received 6 mg/kg MPH, orally, twice each day for 28 d. Rats were then reassessed for impulsivity and underwent a second [18F]fallypride PET scan. Before MPH treatment, we found that D2/3 receptor availability was significantly decreased in the left but not the right ventral striatum of high-impulse (HI) rats compared with low-impulse (LI) rats. MPH treatment increased impulsivity in LI rats, and modulated impulsivity and D2/3 receptor availability in the dorsal and ventral striatum of HI rats through inverse relationships with baseline levels of impulsivity and D2/3 receptor availability, respectively. However, we found no relationship between the effects of MPH on impulsivity and D2/3 receptor availability in any of the striatal subregions investigated. These findings indicate that trait-like impulsivity is associated with decreased D2/3 receptor availability in the left ventral striatum, and that stimulant drugs modulate impulsivity and striatal D2/3 receptor availability through independent mechanisms.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Psychology Schools > Pharmacy
Publisher:	Society for Neuroscience
ISSN:	1529-2401
Last Modified:	02 Jul 2024 01:34
URI:	https://orca.cardiff.ac.uk/id/eprint/162763

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