Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Lack of self-administration of cocaine in dopamine d-1 receptor knock-out mice

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Caine, S. B.
  • Thomsen, M.
  • Gabriel, K. I.
  • Berkowitz, J. S.
  • Gold, L. H.
  • Koob, George
  • Tonegawa, S.
  • Zhang, J. H.
  • Xu, M.

publication date

  • November 2007

journal

  • Journal of Neuroscience  Journal

abstract

  • Evidence suggests a critical role for dopamine in the reinforcing effects of cocaine in rats and primates. However, self-administration has been less often studied in the mouse species, and, to date, "knock-out" of individual dopamine-related genes in mice has not been reported to reduce the reinforcing effects of cocaine. We studied the dopamine D1 receptor and cocaine self-administration in mice using a combination of gene-targeted mutation and pharmacological tools. Two cohorts with varied breeding and experimental histories were tested, and, in both cohorts, there was a significant decrease in the number of D1 receptor knock-out mice that met criteria for acquisition of cocaine self-administration (2 of 23) relative to wild-type mice (27 of 32). After extinction of responding with saline self-administration, dose-response studies showed that cocaine reliably and dose dependently maintained responding greater than saline in all wild-type mice but in none of the D1 receptor knock-out mice. The D1-like agonist SKF 82958 (2,3,4,5,-tetrahydro-6-chloro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrobromide) and the D2-like agonist quinelorane both functioned as positive reinforcers in wild-type mice but not in D1 receptor mutant mice, whereas food and intravenous injections of the opioid agonist remifentanil functioned as positive reinforcers in both genotypes. Finally, pretreatment with the D1-like antagonist SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-01] produced surmountable antagonism of the reinforcing effects of cocaine in the commonly used strain C57BL/6J. We conclude that D1 receptor knock-out mice do not reliably self-administer cocaine and that the D1 receptor is critical for the reinforcing effects of cocaine and other dopamine agonists, but not food or opioids, in mice.

subject areas

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Benzazepines
  • Cocaine
  • Conditioning, Operant
  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Drug Administration Schedule
  • Drug Interactions
  • Hypnotics and Sedatives
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity
  • Piperidines
  • Receptors, Dopamine D1
  • Reinforcement (Psychology)
  • Self Administration
  • Statistics, Nonparametric
scroll to property group menus

Research

keywords

  • D-1
  • cocaine
  • dopamine
  • knock-out
  • mouse
  • self-administration
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.2284-07.2007

PubMed ID

  • 18045908
scroll to property group menus

Additional Document Info

start page

  • 13140

end page

  • 13150

volume

  • 27

issue

  • 48

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support