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Muscarinic receptor agonists decrease cocaine self-administration rates in drug-naive mice.

T Rasmussen1, P Sauerberg, E B Nielsen

  • 1Health Care Discovery, Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Måløv, Denmark.

European Journal of Pharmacology
|August 26, 2000
PubMed
Summary
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Selective muscarinic receptor ligand (PTAC) and agonists reduced cocaine self-administration in mice. This suggests muscarinic receptor agonists may treat cocaine abuse.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Selective muscarinic receptor ligands like (5R,6R)-6-(3-Propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[ 3.2.1]octane (PTAC) interact with various muscarinic receptor subtypes.
  • PTAC has previously shown functional dopamine receptor antagonism in rodents, despite lacking direct dopamine receptor affinity.

Purpose of the Study:

  • To investigate the effect of PTAC and other muscarinic receptor agonists on cocaine self-administration in mice.
  • To explore the potential therapeutic applications of muscarinic receptor modulators in treating cocaine abuse.

Main Methods:

  • Drug-naive mice underwent intravenous self-administration of cocaine under a fixed ratio 1 schedule.
  • The effects of PTAC, muscarinic agonists (pilocarpine, oxotremorine), and dopamine receptor antagonists (olanzapine, clozapine, risperidone, fluphenazine, haloperidol) on cocaine self-administration rates were assessed.

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Main Results:

  • PTAC, pilocarpine, and oxotremorine dose-dependently decreased cocaine self-administration rates.
  • Dopamine receptor antagonists also significantly reduced cocaine self-administration rates, mirroring the effects of muscarinic agonists.

Conclusions:

  • Compounds acting as partial muscarinic receptor agonists demonstrate efficacy in reducing cocaine self-administration.
  • These findings support the potential use of muscarinic receptor agonists in the medical treatment of cocaine abuse.