Hypocretin 1/orexin A in the ventral tegmental area enhances dopamine responses to cocaine and promotes cocaine self-administration.

EspaƱa RA, Melchior JR, Roberts DC, Jones SR
Psychopharmacology (Berl). 2011 214 (2): 415-26

PMID: 20959967 · PMCID: PMC3085140 · DOI:10.1007/s00213-010-2048-8

RATIONALE - Recent evidence indicates that the hypocretin/orexin system participates in the regulation of reinforcement and addiction processes. For example, manipulations that decrease hypocretin neurotransmission result in disruptions of neurochemical and behavioral responses to cocaine.

OBJECTIVES - To further assess the relationship between the hypocretin system and cocaine reinforcement, the current studies used microdialysis and in vivo voltammetry to examine the effects of hypocretin 1 on cocaine-induced enhancement of dopamine signaling in the nucleus accumbens core. Fixed ratio, discrete trials, and progressive ratio self-administration procedures were also used to assess whether hypocretin 1 promotes cocaine self-administration behavior.

RESULTS - Infusions of hypocretin 1 into the ventral tegmental area increased the effects of cocaine on tonic and phasic dopamine signaling and increased the motivation to self-administer cocaine on the discrete trials and progressive ratio schedules.

CONCLUSIONS - Together with previous observations demonstrating that a hypocretin 1 receptor antagonist disrupts dopamine signaling and reduces self-administration of cocaine, the current observations further indicate that the hypocretin system participates in reinforcement processes likely through modulation of the mesolimbic dopamine system.

MeSH Terms (24)

Analysis of Variance Animals Behavior, Addictive Behavior, Animal Central Nervous System Stimulants Cocaine Dopamine Infusions, Parenteral Injections, Intravenous Intracellular Signaling Peptides and Proteins Male Microdialysis Motivation Neuropeptides Orexins Potentiometry Rats Rats, Sprague-Dawley Reinforcement, Psychology Reward Self Administration Signal Transduction Time Factors Ventral Tegmental Area

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