title: Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats.
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.
authors.affiliation: Department of Psychological and Brain Sciences, 64 Cummington Mall, Boston University, Boston, MA 02215, USA.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Gauthier
authors.affiliation: Department of Psychological and Brain Sciences, 64 Cummington Mall, Boston University, Boston, MA 02215, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Tassin
authors.affiliation: Department of Pharmaceutical Sciences, 789 South Limestone, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Linda P
authors.initials: LP
authors.lastname: Dwoskin
authors.affiliation: Department of Psychological and Brain Sciences, 64 Cummington Mall, Boston University, Boston, MA 02215, USA. Electronic address: kkantak@bu.edu.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Kantak
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology* / Q000523:psychology; D001552:Benzazepines / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology*; D056344:Executive Function / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012201:Reward; D013045:Species Specificity; D013647:Task Performance and Analysis
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390
keywords: Attention Deficit Hyperactivity Disorder; Behavioral flexibility; Dopamine D1 receptors; Dorsal striatum; Executive function; Prefrontal cortex; Reward devaluation
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