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Dopamine D1-like and D2-like receptors in the dorsal striatum control different aspects of attentional performance in the five-choice serial reaction time task under a condition of increased activity of corticostriatal inputs.

ABSTRACT: We investigated the interaction between the corticostriatal glutamatergic afferents and dopamine D1-like and D2-like receptors in the dorsomedial striatum (dm-STR) in attention and executive response control in the five-choice serial reaction time (5-CSRT) task. The competitive NMDA receptor antagonist 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) injected in the mPFC impaired accuracy and increased premature and perseverative responding, raising GLU, DA, and GABA release in the dm-STR. The D1-like antagonist SCH23390 injected in the dm-STR reversed the CPP-induced accuracy deficit but did not affect the increase in perseverative responding. In contrast, the D2-like antagonist haloperidol injected in the dm-STR reduced the CPP-induced increase in perseverative responding but not the accuracy deficit. The different roles of dorsal striatal D1-like and D2-like receptor were further supported by the finding that activation of D1-like receptor in the dm-STR by SKF38393 impaired accuracy but not perseverative responding while the D2-like agonist quinpirole injected in the dm-STR increased perseverative responding but did not affect accuracy. These findings suggest that integration of cortical information by D1-like receptors in the dm-STR is a key mechanism of the input selection process of attention while the integration of corticostriatal signals by D2-like receptors preserves the ability to switch from one act/response to the next in a complex motor sequence, thus providing for behavioral flexibility.

SUBMITTER: Agnoli L

PROVIDER: S-EPMC3671986 | biostudies-literature |

REPOSITORIES: biostudies-literature

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| S-EPMC2882949 | biostudies-literature

D1 and D2 dopamine receptors differentially mediate the activation of phosphoproteins in the striatum of amphetamine-sensitized rats.

Project description:RationaleExtracellular signal-regulated kinase (ERK), cAMP response element binding protein (CREB), and protein kinase B (PKB or Akt) in the striatum are differentially activated by acute and repeated amphetamine (AMPH) administration. However, the dopamine receptor subtypes that mediate transient vs. prolonged phosphorylation changes in these proteins induced by AMPH challenge in AMPH-sensitized rats are unknown.ObjectivesThe role of the D1 and D2 class of dopamine receptors in the differential phosphorylation of striatal ERK, CREB, Thr308-Akt and Ser473-Akt and the expression of behavioral sensitization induced by AMPH challenge in AMPH-pretreated rats were determined.MethodsD1 or D2 dopamine receptor antagonists were injected before an AMPH challenge in AMPH-sensitized rats. After behavioral activity was recorded, rats were euthanized either 15 min or 2 h after AMPH challenge and striatal phosphoprotein status was analyzed by Western blotting.ResultsThe D1 receptor antagonist (SCH23390) decreased stereotypical behavior whereas the D2 receptor antagonist (eticlopride) decreased all behavioral activity induced by an AMPH challenge in AMPH-sensitized rats. SCH23390, but not eticlopride, significantly decreased ERK, CREB, and Thr308-Akt phosphorylation in the striatum 15 min, and ERK and CREB phosphorylation 2 h, after AMPH challenge in AMPH-sensitized rats. In contrast, eticlopride, but not SCH23390, prevented a decrease in Akt phosphorylation 2 h after AMPH challenge.ConclusionsThese data indicate that the time course of phosphoprotein signaling is differentially regulated by D1 and D2 receptors in the striatum of AMPH-sensitized rats, suggesting that complex regulatory interactions are activated by repeated AMPH exposure.

| S-EPMC3065836 | biostudies-literature

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