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BDNF is a negative modulator of morphine action.
Ja Wook Koo1, Michelle S Mazei-Robison, Dipesh Chaudhury
1Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Science (New York, N.Y.)
|October 9, 2012
Summary
Brain-derived neurotrophic factor (BDNF) surprisingly counters morphine reward by regulating dopamine neurons in the VTA and NAc. Suppressing BDNF in the VTA enhances morphine
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Brain-derived neurotrophic factor (BDNF) is known to enhance neural plasticity and drug reward.
- Its role in the context of chronic morphine exposure and reward circuitry is not fully understood.
Purpose of the Study:
- To investigate the role of BDNF in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in mediating the effects of chronic morphine exposure.
- To elucidate the molecular mechanisms underlying BDNF's influence on morphine reward and dopamine neuron activity.
Main Methods:
- Utilized genetic suppression of BDNF in the VTA.
- Employed optical stimulation of VTA dopamine (DA) terminals in the NAc.
- Analyzed gene expression in the NAc following chronic morphine exposure and BDNF manipulation.
Main Results:
- Suppression of BDNF in the VTA potentiated morphine's ability to increase DA neuron excitability and promote reward.
- Optical stimulation of VTA DA terminals in the NAc reversed BDNF's suppressive effect on morphine reward.
- Identified specific genes in the NAc regulated by BDNF that mediate its counteractive function in chronic morphine exposure.
Conclusions:
- BDNF plays a critical, counteractive role in regulating the brain's response to chronic morphine exposure.
- These findings reveal novel molecular targets within the VTA-NAc circuitry for understanding and potentially treating morphine addiction.
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