In vivo up-regulation of brain-derived neurotrophic factor in specific brain areas by chronic exposure to Δ9-tetrahydrocannabinol

Elena Butovsky, Ana Juknat, Igor Goncharov, Judith Elbaz, Raya Eilam, Abraham Zangen, Zvi Vogel

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Cannabinoids are widely abused drugs. Here we show that chronic administration of Δ9-tetrahydrocannabinol (Δ9- THC), the active psychotropic agent in marijuana and hashish, at 1.5 mg per kg per day intraperitoneally for 7 days, increases the expression, at both mRNA and protein levels, of brain-derived neurotrophic factor (BDNF), in specific rat brain areas, notably in those involved in reward and addiction. Real-time PCR revealed a 10-fold up-regulation of BDNF mRNA in the nucleus accumbens (NAc) upon chronic Δ9-THC treatment, but there was no change at 3 or 24 h after a single injection. Smaller increases in mRNA levels were found in the ventral tegmental area (VTA), medial prefrontal cortex and paraventricular nucleus (PVN). Immunohistochemistry showed large increases in BDNF-stained cells in the NAc (5.5-fold), posterior VTA (4-fold) and PVN (1.7-fold), but no change was observed in the anterior VTA, hippocampus or dorsal striatum. Altogether, our study indicates that chronic exposure to Δ9-THC up-regulates BDNF in specific brain areas involved with reward, and provides evidence for different BDNF expression in the anterior and posterior VTA. Moreover, BDNF is known to modulate synaptic plasticity and adaptive processes underlying learning and memory, leading to long-term functional and structural modification of synaptic connections. We suggest that Δ9-THC up-regulation of BDNF expression has an important role in inducing the neuroadaptive processes taking place upon exposure to cannabinoids.

Original languageEnglish
Pages (from-to)802-811
Number of pages10
JournalJournal of Neurochemistry
Volume93
Issue number4
DOIs
StatePublished - 1 May 2005
Externally publishedYes

Keywords

  • Brain-derived neurotrophic factor
  • Cannabinoids
  • Nucleus accumbens
  • Posterior ventral tegmental area
  • Reward system
  • Δ- tetrahydrocannabinol

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