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Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice.
Eur J Pharmacol. 2016 Apr 05; 776:71-80.EJ

Abstract

Muscarinic and dopamine brain systems interact intimately, and muscarinic receptor ligands, like dopamine ligands, can modulate the reinforcing and discriminative stimulus (S(D)) effects of cocaine. To enlighten the dopamine/muscarinic interactions as they pertain to the S(D) effects of cocaine, we evaluated whether muscarinic M1, M2 or M4 receptors are necessary for dopamine D1 and/or D2 antagonist mediated modulation of the S(D) effects of cocaine. Knockout mice lacking M1, M2, or M4 receptors, as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline in a food-reinforced drug discrimination procedure. Effects of pretreatments with the dopamine D1 antagonist SCH 23390 and the dopamine D2 antagonist eticlopride were evaluated. In intact mice, both SCH 23390 and eticlopride attenuated the cocaine discriminative stimulus effect, as expected. SCH 23390 similarly attenuated the cocaine discriminative stimulus effect in M1 knockout mice, but not in mice lacking M2 or M4 receptors. The effects of eticlopride were comparable in each knockout strain. These findings demonstrate differences in the way that D1 and D2 antagonists modulate the S(D) effects of cocaine, D1 modulation being at least partially dependent upon activity at the inhibitory M2/M4 muscarinic subtypes, while D2 modulation appeared independent of these systems.

Authors+Show Affiliations

Alcohol and Drug Abuse Research Center, McLean Hospital/Harvard Medical School, Belmont, MA, United States. Electronic address: mthomsen@mclean.harvard.edu.Alcohol and Drug Abuse Research Center, McLean Hospital/Harvard Medical School, Belmont, MA, United States. Electronic address: sbarak@mclean.harvard.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26874213

Citation

Thomsen, Morgane, and Simon Barak Caine. "Effects of Dopamine D1-like and D2-like Antagonists On Cocaine Discrimination in Muscarinic Receptor Knockout Mice." European Journal of Pharmacology, vol. 776, 2016, pp. 71-80.
Thomsen M, Caine SB. Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice. Eur J Pharmacol. 2016;776:71-80.
Thomsen, M., & Caine, S. B. (2016). Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice. European Journal of Pharmacology, 776, 71-80. https://doi.org/10.1016/j.ejphar.2016.02.034
Thomsen M, Caine SB. Effects of Dopamine D1-like and D2-like Antagonists On Cocaine Discrimination in Muscarinic Receptor Knockout Mice. Eur J Pharmacol. 2016 Apr 5;776:71-80. PubMed PMID: 26874213.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice. AU - Thomsen,Morgane, AU - Caine,Simon Barak, Y1 - 2016/02/11/ PY - 2015/10/05/received PY - 2016/02/08/revised PY - 2016/02/10/accepted PY - 2016/2/14/entrez PY - 2016/2/14/pubmed PY - 2016/12/15/medline KW - D1 KW - D2 KW - Dopamine receptors KW - Drug discrimination KW - Knockout mice KW - M1 KW - M2 KW - M4 KW - Muscarinic receptors SP - 71 EP - 80 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 776 N2 - Muscarinic and dopamine brain systems interact intimately, and muscarinic receptor ligands, like dopamine ligands, can modulate the reinforcing and discriminative stimulus (S(D)) effects of cocaine. To enlighten the dopamine/muscarinic interactions as they pertain to the S(D) effects of cocaine, we evaluated whether muscarinic M1, M2 or M4 receptors are necessary for dopamine D1 and/or D2 antagonist mediated modulation of the S(D) effects of cocaine. Knockout mice lacking M1, M2, or M4 receptors, as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline in a food-reinforced drug discrimination procedure. Effects of pretreatments with the dopamine D1 antagonist SCH 23390 and the dopamine D2 antagonist eticlopride were evaluated. In intact mice, both SCH 23390 and eticlopride attenuated the cocaine discriminative stimulus effect, as expected. SCH 23390 similarly attenuated the cocaine discriminative stimulus effect in M1 knockout mice, but not in mice lacking M2 or M4 receptors. The effects of eticlopride were comparable in each knockout strain. These findings demonstrate differences in the way that D1 and D2 antagonists modulate the S(D) effects of cocaine, D1 modulation being at least partially dependent upon activity at the inhibitory M2/M4 muscarinic subtypes, while D2 modulation appeared independent of these systems. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/26874213/Effects_of_dopamine_D1_like_and_D2_like_antagonists_on_cocaine_discrimination_in_muscarinic_receptor_knockout_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(16)30062-0 DB - PRIME DP - Unbound Medicine ER -