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Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats.


ABSTRACT: The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1 h; ShA) or long- (12 h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence.

SUBMITTER: Schmeichel BE 

PROVIDER: S-EPMC4367454 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats.

Schmeichel Brooke E BE   Barbier Estelle E   Misra Kaushik K KK   Contet Candice C   Schlosburg Joel E JE   Grigoriadis Dimitri D   Williams John P JP   Karlsson Camilla C   Pitcairn Caleb C   Heilig Markus M   Koob George F GF   Vendruscolo Leandro F LF  

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20150313 5


The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like  ...[more]

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