The number of lateral hypothalamus orexin/hypocretin neurons contributes to individual differences in cocaine demand

Caroline B. Pantazis, Morgan H. James, Brandon S. Bentzley, Gary Aston-Jones

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Lateral hypothalamus (LH) orexin neuron signaling has been implicated in the motivation to seek and take drugs of abuse. The number of LH orexin neurons has been shown to be upregulated with exposure to drugs of abuse. We sought to determine if the number of LH orexin neurons related to individual differences in motivation (demand) for cocaine in our behavioral economics (BE) paradigm, and whether knockdown of these cells predicted changes in economic demand. We quantified LH orexin cell numbers in animals immediately following our BE paradigm, as well as after a 2-week period of abstinence, to relate the number of LH orexin cells to economic demand for cocaine. We also knocked down LH orexin expression with an orexin morpholino antisense to determine how reduced orexin numbers impacted cocaine demand. We found that animals with greater baseline motivation for cocaine (lower demand elasticity) had more LH orexin neurons. Following a 2-week abstinence from cocaine, the number of LH orexin neurons predicted economic demand for cocaine prior to abstinence, indicating that orexin expression is a persistent marker for demand. Reducing LH orexin cell numbers with antisense decreased motivation for cocaine (increased demand elasticity) without affecting baseline consumption. In addition, the number of spared LH orexin neurons after antisense treatment correlated with individual motivation for cocaine. These studies point to a role for the endogenous number of LH orexin neurons in individual differences in motivation for cocaine.

Original languageEnglish (US)
Article numbere12795
JournalAddiction Biology
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Lateral Hypothalamic Area
Cocaine
Individuality
Neurons
Motivation
Behavioral Economics
Economics
Elasticity
Street Drugs
Orexins
Cell Count
Morpholinos

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

Keywords

  • behavioral economics
  • hypothalamus
  • motivation

Cite this

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title = "The number of lateral hypothalamus orexin/hypocretin neurons contributes to individual differences in cocaine demand",
abstract = "Lateral hypothalamus (LH) orexin neuron signaling has been implicated in the motivation to seek and take drugs of abuse. The number of LH orexin neurons has been shown to be upregulated with exposure to drugs of abuse. We sought to determine if the number of LH orexin neurons related to individual differences in motivation (demand) for cocaine in our behavioral economics (BE) paradigm, and whether knockdown of these cells predicted changes in economic demand. We quantified LH orexin cell numbers in animals immediately following our BE paradigm, as well as after a 2-week period of abstinence, to relate the number of LH orexin cells to economic demand for cocaine. We also knocked down LH orexin expression with an orexin morpholino antisense to determine how reduced orexin numbers impacted cocaine demand. We found that animals with greater baseline motivation for cocaine (lower demand elasticity) had more LH orexin neurons. Following a 2-week abstinence from cocaine, the number of LH orexin neurons predicted economic demand for cocaine prior to abstinence, indicating that orexin expression is a persistent marker for demand. Reducing LH orexin cell numbers with antisense decreased motivation for cocaine (increased demand elasticity) without affecting baseline consumption. In addition, the number of spared LH orexin neurons after antisense treatment correlated with individual motivation for cocaine. These studies point to a role for the endogenous number of LH orexin neurons in individual differences in motivation for cocaine.",
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The number of lateral hypothalamus orexin/hypocretin neurons contributes to individual differences in cocaine demand. / Pantazis, Caroline B.; James, Morgan H.; Bentzley, Brandon S.; Aston-Jones, Gary.

In: Addiction Biology, 01.01.2019.

Research output: Contribution to journalArticle

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