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D1 and D2 dopamine receptors differentially mediate the activation of phosphoproteins in the striatum of amphetamine-sensitized rats.
Psychopharmacology (Berl). 2011 Apr; 214(3):653-63.P

Abstract

RATIONALE

Extracellular 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.

OBJECTIVES

The 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.

METHODS

D1 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.

RESULTS

The 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.

CONCLUSIONS

These 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.

Authors+Show Affiliations

Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue MSC 510, Charleston, SC 29425, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21057772

Citation

Shi, Xiangdang, and Jacqueline F. McGinty. "D1 and D2 Dopamine Receptors Differentially Mediate the Activation of Phosphoproteins in the Striatum of Amphetamine-sensitized Rats." Psychopharmacology, vol. 214, no. 3, 2011, pp. 653-63.
Shi X, McGinty JF. D1 and D2 dopamine receptors differentially mediate the activation of phosphoproteins in the striatum of amphetamine-sensitized rats. Psychopharmacology (Berl). 2011;214(3):653-63.
Shi, X., & McGinty, J. F. (2011). D1 and D2 dopamine receptors differentially mediate the activation of phosphoproteins in the striatum of amphetamine-sensitized rats. Psychopharmacology, 214(3), 653-63. https://doi.org/10.1007/s00213-010-2068-4
Shi X, McGinty JF. D1 and D2 Dopamine Receptors Differentially Mediate the Activation of Phosphoproteins in the Striatum of Amphetamine-sensitized Rats. Psychopharmacology (Berl). 2011;214(3):653-63. PubMed PMID: 21057772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - D1 and D2 dopamine receptors differentially mediate the activation of phosphoproteins in the striatum of amphetamine-sensitized rats. AU - Shi,Xiangdang, AU - McGinty,Jacqueline F, Y1 - 2010/11/06/ PY - 2010/08/31/received PY - 2010/10/20/accepted PY - 2010/11/9/entrez PY - 2010/11/9/pubmed PY - 2011/7/16/medline SP - 653 EP - 63 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 214 IS - 3 N2 - RATIONALE: Extracellular 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. OBJECTIVES: The 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. METHODS: D1 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. RESULTS: The 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. CONCLUSIONS: These 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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/21057772/D1_and_D2_dopamine_receptors_differentially_mediate_the_activation_of_phosphoproteins_in_the_striatum_of_amphetamine_sensitized_rats_ DB - PRIME DP - Unbound Medicine ER -