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Hypocretin/orexin antagonists decrease cocaine self-administration by female rhesus monkeys.

Richard W Foltin1, Suzette M Evans1

  • 1Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, Unit 120, New York, NY, 10032, USA.

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PubMed
Summary
This summary is machine-generated.

The hypocretin receptor-1 (HCRTr1) antagonist SB-334867 reduced cocaine intake in rhesus monkeys across multiple schedules. This suggests the hypocretin system

Keywords:
AmphetamineCocaineFemaleHypocretinNon-human primateOrexinRhesus monkeySelf-administration

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • The hypocretin/orexin system regulates arousal and influences appetitive behaviors.
  • Hypocretin receptor-1 (HCRTr1) antagonists have shown potential in reducing stimulant drug self-administration and reinstatement.

Purpose of the Study:

  • To investigate the effects of hypocretin-1 and HCRTr1 antagonists on cocaine self-administration in female rhesus monkeys.
  • To examine these effects under various reinforcement schedules, including fixed interval/fixed ratio, progressive ratio, and choice tasks.

Main Methods:

  • Five female rhesus monkeys underwent intravenous cocaine self-administration training.
  • The HCRTr1 antagonist SB-334867 and d-amphetamine were administered via intramuscular injection.
  • Cocaine intake was assessed under fixed interval-fixed ratio, progressive ratio, and choice schedules; hypocretin-1 was administered intravenously.

Main Results:

  • The HCRTr1 antagonist SB-334867 significantly decreased cocaine intake across multiple schedules.
  • d-amphetamine also reduced cocaine intake under the fixed interval/fixed ratio schedule.
  • Intravenous hypocretin-1 increased cocaine intake in some monkeys, and SB-334867 attenuated cocaine reinstatement.

Conclusions:

  • The hypocretin system modulates responses to appetitive stimuli, extending findings from male rodents to female non-human primates.
  • Understanding the hypocretin system's role offers potential for novel medication development for appetitive disorders.