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The dopamine D1-D2 receptor heteromer exerts a tonic inhibitory effect on the expression of amphetamine-induced locomotor sensitization.
Pharmacol Biochem Behav. 2015 Jan; 128:33-40.PB

Abstract

A role for the dopamine D1-D2 receptor heteromer in the regulation of reward and addiction-related processes has been previously implicated. In the present study, we examined the effects of D1-D2 heteromer stimulation by the agonist SKF 83959 and its disruption by a selective TAT-D1 peptide on amphetamine-induced locomotor sensitization, a behavioral model widely used to study the neuroadaptations associated with psychostimulant addiction. D1-D2 heteromer activation by SKF 83959 did not alter the acute locomotor effects of amphetamine but significantly inhibited amphetamine-induced locomotor responding across the 5day treatment regimen. In addition, a single injection of SKF 83959 was sufficient to abolish the expression of locomotor sensitization induced by a priming injection of amphetamine after a 72-hour withdrawal. Conversely, inhibition of D1-D2 heteromer activity by the TAT-D1 peptide enhanced subchronic amphetamine-induced locomotion and the expression of amphetamine locomotor sensitization. Treatment solely with the TAT-D1 disrupting peptide during the initial 5day treatment phase was sufficient to induce a sensitized locomotor phenotype in response to the priming injection of amphetamine. Together these findings demonstrate that the dopamine D1-D2 receptor heteromer exerts a tonic inhibitory control on neurobiological processes involved in sensitization to amphetamine, indicating that the dopamine D1-D2 receptor heteromer may be a novel molecular substrate in addiction processes involving psychostimulants.

Authors+Show Affiliations

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: s.george@utoronto.ca.

Pub Type(s)

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

Language

eng

PubMed ID

25444866

Citation

Shen, Maurice Y F., et al. "The Dopamine D1-D2 Receptor Heteromer Exerts a Tonic Inhibitory Effect On the Expression of Amphetamine-induced Locomotor Sensitization." Pharmacology, Biochemistry, and Behavior, vol. 128, 2015, pp. 33-40.
Shen MY, Perreault ML, Fan T, et al. The dopamine D1-D2 receptor heteromer exerts a tonic inhibitory effect on the expression of amphetamine-induced locomotor sensitization. Pharmacol Biochem Behav. 2015;128:33-40.
Shen, M. Y., Perreault, M. L., Fan, T., & George, S. R. (2015). The dopamine D1-D2 receptor heteromer exerts a tonic inhibitory effect on the expression of amphetamine-induced locomotor sensitization. Pharmacology, Biochemistry, and Behavior, 128, 33-40. https://doi.org/10.1016/j.pbb.2014.11.011
Shen MY, et al. The Dopamine D1-D2 Receptor Heteromer Exerts a Tonic Inhibitory Effect On the Expression of Amphetamine-induced Locomotor Sensitization. Pharmacol Biochem Behav. 2015;128:33-40. PubMed PMID: 25444866.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The dopamine D1-D2 receptor heteromer exerts a tonic inhibitory effect on the expression of amphetamine-induced locomotor sensitization. AU - Shen,Maurice Y F, AU - Perreault,Melissa L, AU - Fan,Theresa, AU - George,Susan R, Y1 - 2014/11/13/ PY - 2014/09/27/received PY - 2014/11/04/revised PY - 2014/11/08/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/9/17/medline KW - Amphetamine KW - Dopamine D1–D2 receptor heteromer KW - Locomotor sensitization SP - 33 EP - 40 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 128 N2 - A role for the dopamine D1-D2 receptor heteromer in the regulation of reward and addiction-related processes has been previously implicated. In the present study, we examined the effects of D1-D2 heteromer stimulation by the agonist SKF 83959 and its disruption by a selective TAT-D1 peptide on amphetamine-induced locomotor sensitization, a behavioral model widely used to study the neuroadaptations associated with psychostimulant addiction. D1-D2 heteromer activation by SKF 83959 did not alter the acute locomotor effects of amphetamine but significantly inhibited amphetamine-induced locomotor responding across the 5day treatment regimen. In addition, a single injection of SKF 83959 was sufficient to abolish the expression of locomotor sensitization induced by a priming injection of amphetamine after a 72-hour withdrawal. Conversely, inhibition of D1-D2 heteromer activity by the TAT-D1 peptide enhanced subchronic amphetamine-induced locomotion and the expression of amphetamine locomotor sensitization. Treatment solely with the TAT-D1 disrupting peptide during the initial 5day treatment phase was sufficient to induce a sensitized locomotor phenotype in response to the priming injection of amphetamine. Together these findings demonstrate that the dopamine D1-D2 receptor heteromer exerts a tonic inhibitory control on neurobiological processes involved in sensitization to amphetamine, indicating that the dopamine D1-D2 receptor heteromer may be a novel molecular substrate in addiction processes involving psychostimulants. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/25444866/The_dopamine_D1_D2_receptor_heteromer_exerts_a_tonic_inhibitory_effect_on_the_expression_of_amphetamine_induced_locomotor_sensitization_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(14)00304-9 DB - PRIME DP - Unbound Medicine ER -