Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in wistar and spontaneously hypertensive rats

Jamie M. Gauthier, David H. Tassin, Linda P. Dwoskin, Kathleen M. Kantak

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is associated with dysfunctional prefrontal and striatal circuitry and dysregulated dopamine neurotransmission. Spontaneously Hypertensive Rats (SHR), a heuristically useful animal model of ADHD, were evaluated against normotensive Wistar (WIS) controls to determine whether dopamine D1 receptor blockade of either prelimbic prefrontal cortex (plPFC) or lateral dorsal striatum (lDST) altered learning functions of both interconnected sites. A strategy set shifting task measured plPFC function (behavioral flexibility/executive function) and a reward devaluation task measured lDST function (habitual responding). Prior to tests, rats received bilateral infusions of SCH 23390 (1.0. μg/side) or vehicle into plPFC or lDST. Following vehicle, SHR exhibited longer lever press reaction times, more trial omissions, and fewer completed trials during the set shift test compared to WIS, indicating slower decision-making and attentional/motivational impairment in SHR. After reward devaluation, vehicle-treated SHR responded less than WIS, indicating relatively less habitual responding in SHR. After SCH 23390 infusions into plPFC, WIS expressed the same behavioral phenotype as vehicle-treated SHR during set shift and reward devaluation tests. In SHR, SCH 23390 infusions into plPFC exacerbated behavioral deficits in the set shift test and maintained the lower rate of responding in the reward devaluation test. SCH 23390 infusions into lDST did not modify set shifting in either strain, but produced lower rates of responding than vehicle infusions after reward devaluation in WIS. This research provides pharmacological evidence for unidirectional interactions between prefrontal and striatal brain regions, which has implications for the neurological basis of ADHD and its treatment.

Original languageEnglish
Pages (from-to)229-238
Number of pages10
JournalBehavioural Brain Research
Volume268
DOIs
StatePublished - Jul 15 2014

Bibliographical note

Funding Information:
The authors declare no competing financial interests. This study was supported by NSF grant SMA 0835976 to the CELEST Science of Learning Center and National Institute of Health grant DA011716 .

Keywords

  • Attention Deficit Hyperactivity Disorder
  • Behavioral flexibility
  • Dopamine D1 receptors
  • Dorsal striatum
  • Executive function
  • Prefrontal cortex
  • Reward devaluation

ASJC Scopus subject areas

  • Behavioral Neuroscience

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