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In vivo up‐regulation of brain‐derived neurotrophic factor in specific brain areas by chronic exposure to Δ 9 ‐tetrahydrocannabinol
Author(s) -
Butovsky Elena,
Juknat Ana,
Goncharov Igor,
Elbaz Judith,
Eilam Raya,
Zangen Abraham,
Vogel Zvi
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03074.x
Subject(s) - nucleus accumbens , ventral tegmental area , prefrontal cortex , neuroscience , brain derived neurotrophic factor , hippocampus , striatum , neurotrophic factors , synaptic plasticity , medicine , endocrinology , psychology , chemistry , biology , central nervous system , dopamine , receptor , cognition , dopaminergic
Cannabinoids are widely abused drugs. Here we show that chronic administration of Δ 9 ‐tetrahydrocannabinol (Δ 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 Δ 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 Δ 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 Δ 9 ‐THC up‐regulation of BDNF expression has an important role in inducing the neuroadaptive processes taking place upon exposure to cannabinoids.