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The corticotropin-releasing factor receptor-2 mediates the motivational effect of opiate withdrawal

Khalil Rouibi1, Angelo Contarino

  • 1Univ. Bordeaux, INCIA, UMR 5287, F-33000 Bordeaux, France.

Neuropharmacology
|May 28, 2013
PubMed

Insights

Genetic disruption of corticotropin-releasing factor receptor-2 (CRF₂) does not affect baseline motivation but reduces opiate withdrawal-induced increases in food motivation in mice.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Altered motivation is central to drug dependence and withdrawal.
  • Neural mechanisms underlying these motivational changes are not well understood.
  • Corticotropin-releasing factor (CRF) system involvement in stress and addiction is implicated.

Purpose of the Study:

  • To investigate the role of the CRF₂ receptor in motivational processes during opiate withdrawal.
  • To determine if CRF₂ receptor deficiency impacts motivation for palatable food in drug-naïve or morphine-withdrawn mice.
  • To assess the specificity of CRF₂ receptor's role in withdrawal-induced motivational changes.

Main Methods:

  • Utilized genetically modified mice lacking the CRF₂ receptor (CRF₂-/-).
  • Assessed motivation for palatable food using a progressive ratio (PR) operant schedule.
  • Administered escalating doses of morphine to induce withdrawal.
  • Evaluated cognitive function (behavioral discrimination) and general effects (ambulation, body weight).

Main Results:

  • CRF₂ receptor deficiency did not impair motivation for palatable food in drug-naïve mice.
  • Morphine withdrawal significantly increased palatable food motivation in wild-type mice for 6 days.
  • CRF₂-/- mice exhibited blunted and shorter-lasting (2 days) increases in motivation post-withdrawal.
  • Cognitive function and general physiological effects of morphine were unaffected by CRF₂ receptor deficiency.

Conclusions:

  • The CRF₂ receptor plays a specific, gender-independent role in mediating the increased motivation associated with opiate withdrawal.
  • CRF₂ receptor deficiency attenuates, but does not abolish, withdrawal-induced hyperphagia.
  • These findings highlight the CRF₂ receptor as a potential therapeutic target for modulating motivational aspects of opioid use disorder.
Keywords:
ANOVACRFCRF(1)CRF(2)CRF(2) receptorCTLCorticotropin-releasing factor (CRF) systemDrug dependenceFRMotivationNull mutant miceOWOpiate withdrawalPRanalysis of variancecontrolcorticotropin-releasing factorcorticotropin-releasing factor receptor-1corticotropin-releasing factor receptor-2fixed ratioi.p.intraperitoneallyopiate-withdrawnprogressive ratio

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