MPTP-induced executive dysfunction is associated with altered prefrontal serotonergic function

Panchanan Maiti, Laura C. Gregg, Michael Mcdonald

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

In Parkinson's disease, cognitive deficits manifest as fronto-striatally-mediated executive dysfunction, with impaired attention, planning, judgment, and impulse control. We examined changes in executive function in mice lesioned with subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a 3-choice serial reaction-time (SRT) task, which included measures of sustained attention and impulse control. Each trial of the baseline SRT task comprised a pseudo-random pre-cue period ranging from 3 to 8 s, followed by a 1-s cue duration. MPTP impaired all measures of impulsive behavior acutely, but with additional training their performance normalized to saline control levels. When challenged with shorter cue durations, MPTP-lesioned mice had significantly slower reaction times than wild-type mice. When challenged with longer pre-cue times, the MPTP-lesioned mice exhibited a loss of impulse control at the longer durations. In lesioned mice, striatal dopamine was depleted by 54% and the number of tyrosine-hydroxylase-positive neurons in the substantia nigra pars compacta was reduced by 75%. Serotonin (5-HT) was unchanged in the striatum and prefrontal cortex (PFC), but the ratio of 5-hydroxyindolacetic acid (5-HIAA) to 5-HT was significantly reduced in the MPTP group in the PFC. In lesioned mice, prefrontal 5-HIAA/5-HT was significantly correlated with the executive impairments and striatal norepinephrine was associated with slower reaction times. None of the neurochemical measures was significantly associated with behavior in saline-treated controls. Taken together, these results show that prefrontal 5-HT turnover may play a pivotal role in MPTP-induced executive dysfunction.

Original languageEnglish (US)
Pages (from-to)192-201
Number of pages10
JournalBehavioural Brain Research
Volume298
DOIs
StatePublished - Feb 1 2016

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Serotonin
Reaction Time
Cues
Corpus Striatum
Prefrontal Cortex
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Acids
Impulsive Behavior
Executive Function
Tyrosine 3-Monooxygenase
Parkinson Disease
4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine
Norepinephrine
Neurons

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

MPTP-induced executive dysfunction is associated with altered prefrontal serotonergic function. / Maiti, Panchanan; Gregg, Laura C.; Mcdonald, Michael.

In: Behavioural Brain Research, Vol. 298, 01.02.2016, p. 192-201.

Research output: Contribution to journalArticle

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