Chronic exposure to Δ9-tetrahydrocannabinol downregulates oxytocin and oxytocin-associated neurophysin in specific brain areas

Elena Butovsky, Ana Juknat, Judith Elbaz, Maytal Shabat-Simon, Raya Eilam, Abraham Zangen, Miriam Altstein, Zvi Vogel

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Cannabinoids are widely abused drugs. Our goal was to identify genes modulated by Δ9-tetrahydrocannabinol (Δ9-THC) treatment. We found that chronic administration of Δ9-THC (1.5 mg/kg/day, i.p.; 7 days) to rats, downregulates the expression of oxytocin-neurophysin (OT-NP) mRNA and of OT and oxytocin-associated NP (NP OT) immunoreactivity in nucleus accumbens (NAc) and ventral tegmental area (VTA), brain areas involved in reward and addiction. Real-time PCR revealed a 60% and 53% reduction of OT-NP mRNA in NAc and VTA, respectively, under chronic treatment, while no changes were observed in NAc after 24 h. Immunohistochemistry showed a large decrease in number of OT and NP OT-stained fibers in NAc (by 59% and 52%, respectively) and VTA (by 50% and 56%, respectively). No changes in cell staining were observed in the paraventricular nucleus and supraoptic nucleus. As OT is known to inhibit development of drug tolerance and attenuate withdrawal symptoms, we suggest that OT downregulation could play a role during the establishment of the chronic effects of Δ9-THC.

Original languageEnglish
Pages (from-to)795-804
Number of pages10
JournalMolecular and Cellular Neurosciences
Volume31
Issue number4
DOIs
StatePublished - 1 Apr 2006
Externally publishedYes

Keywords

  • Cannabinoids
  • Neurophysin
  • Nucleus accumbens
  • Oxytocin
  • Reward system
  • Ventral tegmental area
  • Δ-THC

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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