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

Cannabinoids are widely abused drugs. Here we show that chronic administration of Delta(9)-tetrahydrocannabinol (Delta(9)-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...

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Bibliographic Details
Published in:Journal of neurochemistry 2005-05, Vol.93 (4), p.802-811
Main Authors: Butovsky, Elena, Juknat, Ana, Goncharov, Igor, Elbaz, Judith, Eilam, Raya, Zangen, Abraham, Vogel, Zvi
Format: Article
Language:English
Subjects:
Animals
Blotting, Northern - methods
Brain - anatomy & histology
Brain - drug effects
Brain - metabolism
Brain-Derived Neurotrophic Factor - genetics
Brain-Derived Neurotrophic Factor - metabolism
Cell Count - methods
Dronabinol - pharmacology
Gene Expression Regulation - drug effects
Immunohistochemistry - methods
Male
Psychotropic Drugs - pharmacology
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction - methods
RNA, Messenger - biosynthesis
Time Factors
Up-Regulation - drug effects
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Summary:Cannabinoids are widely abused drugs. Here we show that chronic administration of Delta(9)-tetrahydrocannabinol (Delta(9)-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 Delta(9)-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 Delta(9)-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 Delta(9)-THC up-regulation of BDNF expression has an important role in inducing the neuroadaptive processes taking place upon exposure to cannabinoids.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2005.03074.x