Anti-obesity drugs that work by blocking brain molecules similar to those in marijuana could also interfere with neural development in young children, according to a new study from MIT's Picower Institute for Learning and Memory.
Marijuana is known to be an appetite stimulant, and a new class of anti-obesity drugs--such as rimonabant (trade name Acomplia) developed by Sanofi-Aventis and awaiting approval for use in the United States--work by blocking brain receptors that bind to marijuana and other cannabinoids.
Marijuana, derived from the plant Cannabis sativa, contains special active compounds that are referred to collectively as cannabinoids. But other cannabinoids (endocannabinoids) are generated naturally inside the body.
The MIT study, which was done in mice, found that blocking cannabinoid receptors could also suppress the adaptive rewiring of the brain necessary for neural development in children. The work is reported in the May 8 issue of Neuron.
"Our finding of a profound disruption of cortical plasticity in juvenile mice suggests caution is advised in the use of such compounds in children," wrote lead author Mark F. Bear, director of the Picower Institute and Picower Professor of Neuroscience.
The researchers investigated plasticity--the brain's ability to change in response to experience--by temporarily depriving newborn mice of vision in one eye soon after birth. This well-known experiment induces a long-lasting loss of synapses that causes blindness in the covered eye, while synapses shift to the uncovered eye. How and where this synaptic shift occurs in the primary visual cortex has remained controversial.
Understanding the mechanism behind this phenomenon is key because the same brain mechanisms are used for normal development and may go awry in conditions that cause developmental delays in humans, and may reappear in old age and contribute to synaptic loss during Alzheimer's disease, Bear said.
In mice, the MIT researchers found, even one day of deprivation from one eye starts the shift to dominance of the uncovered eye. But injecting the mice with a cannabinoid receptor blocker halted the shift in certain brain regions, indicating that cannabinoids play a key role in early synaptic development.
Blocking cannabinoids receptors could thwart this developmental process, the researchers said.
This work is supported by the National Eye Institute and the National Institute of Mental Health.
- Cheng-Hang Liu, Arnold J. Heynen, Marshall G. Hussain Shuler, and Mark F. Bear. Cannabinoid Receptor Blockade Reveals Parallel Plasticity Mechanisms in Different Layers of Mouse Visual Cortex. Neuron 2008 58: 340-345. [link]
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