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Adrenergic Agonists: Indirect-Acting Agents01:25

Adrenergic Agonists: Indirect-Acting Agents

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Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase, which converts...
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Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

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Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
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The dopamine D3 receptor partial agonist CJB090 and antagonist PG01037 decrease progressive ratio responding for

Laura Orio1, Sunmee Wee, Amy H Newman

  • 1The Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA. lorio@scripps.edu

Addiction Biology
|May 12, 2010
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Dopamine D3 receptor modulation affected methamphetamine intake differently based on access duration. Extended access to methamphetamine made rats more sensitive to D3 receptor antagonists and partial agonists.

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Published on: September 21, 2017

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Dopamine D3 receptors are implicated in psychostimulant reinforcement.
  • Selective dopamine D3 receptor compounds offer new avenues for studying psychostimulant dependence.

Purpose of the Study:

  • To investigate the effects of a D3 partial agonist (CJB090) and a D3 antagonist (PG01037) on methamphetamine self-administration in rats.
  • To compare these effects under limited (ShA) versus extended (LgA) access conditions and across fixed (FR) and progressive (PR) ratio schedules.

Main Methods:

  • Rats underwent limited or extended access to intravenous methamphetamine self-administration.
  • The D3 partial agonist CJB090 and D3 antagonist PG01037 were administered intravenously or subcutaneously.
  • Methamphetamine intake was assessed under FR1 and PR schedules of reinforcement.

Main Results:

  • The D3 partial agonist CJB090 reduced methamphetamine intake under FR1 in LgA rats but not ShA rats.
  • Under PR, CJB090 reduced the breakpoint for methamphetamine in both LgA and ShA rats.
  • The D3 antagonist PG01037 had limited effects, primarily reducing PR self-administration in LgA rats at the highest dose.

Conclusions:

  • Extended access to methamphetamine self-administration may increase sensitivity to D3 receptor modulation.
  • Dopamine D3 receptors could play a role in excessive methamphetamine consumption, particularly under conditions of prolonged exposure.