Effects of the trace amine associated receptor 1 agonist RO5263397 on abuse-related behavioral indices of methamphetamine in rats.

Abstract

BACKGROUND:

Methamphetamine is a major drug of abuse with no effective pharmacotherapy available. Trace amine associated receptor 1 is implicated in cocaine addiction and represents a potential therapeutic target. However, the effects of trace amine associated receptor 1 agonists on addiction-related behavioral effects of methamphetamine are unknown.

METHODS:

This study examined the effects of a trace amine associated receptor 1 agonist RO5263397 on methamphetamine-induced behavioral sensitization, methamphetamine self-administration, cue- and methamphetamine-induced reinstatement of drug seeking, and cue-induced reinstatement of sucrose-seeking behaviors in rats. Male Sprague-Dawley rats were used to examine the effects of methamphetamine alone and in combination with the trace amine associated receptor 1 agonist RO5263397 (3.2-10mg/kg).

RESULTS:

RO5263397 dose-dependently attenuated the expression of behavioral sensitization to methamphetamine, reduced methamphetamine self-administration, and decreased both cue- and a priming dose of methamphetamine-induced reinstatement of drug-seeking behaviors. However, RO5263397 did not alter cue-induced reinstatement of sucrose-seeking behavior.

CONCLUSIONS:

Taken together, trace amine associated receptor 1 agonists attenuate some abuse-related behavioral effects of methamphetamine, strongly suggesting that drugs activating trace amine associated receptor 1 may be potentially useful for the treatment of methamphetamine addiction and warrant further studies.

• Authors: Li Jing, Yanan Zhang, Jun-Xu Li
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 18 Issue 4 (Oct 31 2014) ISSN: 1469-5111 [Electronic] England
• PMID: 25522401 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of CINP.

Chemical References

• 4-(3-fluoro-2-methylphenyl)-4,5-dihydrooxazol-2-ylamine
• Central Nervous System Stimulants
• Dietary Sucrose
• Oxazoles
• Receptors, G-Protein-Coupled
• Methamphetamine
• Trace amine-associated receptor 1

Topics

• Akathisia, Drug-Induced (drug therapy, physiopathology)
• Amphetamine-Related Disorders (drug therapy, physiopathology)
• Animals
• Behavior, Addictive (drug therapy, physiopathology)
• Central Nervous System Stimulants (administration & dosage)
• Cues
• Dietary Sucrose (administration & dosage)
• Dose-Response Relationship, Drug
• Drug-Seeking Behavior (drug effects, physiology)
• Male
• Methamphetamine (administration & dosage)
• Oxazoles (pharmacology)
• Rats, Sprague-Dawley
• Receptors, G-Protein-Coupled (agonists, metabolism)
• Self Administration