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Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
BDNF-dependent synaptic sensitization in midbrain dopamine neurons after cocaine withdrawal
Lu Pu1, Qing-song Liu, Mu-ming Poo
1Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA.
Nature Neuroscience
|April 25, 2006
Summary
After cocaine withdrawal, brain-derived neurotrophic factor (BDNF) primes dopamine neuron synapses in the VTA. This priming increases susceptibility to potentiation, potentially triggering drug relapse.
Area of Science:
- Neuroscience
- Neurobiology of Addiction
- Synaptic Plasticity
Background:
- The neural basis of relapse to drug use following withdrawal remains poorly understood.
- Dopamine neurons in the ventral tegmental area (VTA) play a critical role in reward and motivation, and are implicated in addiction.
Purpose of the Study:
- To investigate the synaptic changes in VTA dopamine neurons after cocaine withdrawal.
- To identify the molecular mechanisms contributing to the heightened susceptibility of these synapses.
Main Methods:
- Electrophysiological recordings in rat midbrain slices to assess synaptic plasticity.
- Manipulation of brain-derived neurotrophic factor-tyrosine kinase B (BDNF-TrkB) signaling pathways.
- Assessment of BDNF expression levels in the VTA following chronic cocaine exposure and withdrawal.
Main Results:
- Excitatory synapses onto VTA dopamine neurons exhibit increased susceptibility to long-term potentiation (LTP) after cocaine withdrawal.
- This enhanced synaptic potentiation is dependent on endogenous brain-derived neurotrophic factor-tyrosine kinase B (BDNF-TrkB) signaling.
- Cocaine withdrawal leads to elevated BDNF expression in the VTA.
Conclusions:
- Withdrawal from repeated cocaine exposure induces a state of heightened synaptic plasticity in VTA dopamine neurons.
- Elevated BDNF-TrkB signaling following cocaine withdrawal may prime synapses for potentiation by drug-associated cues.
- This synaptic priming mechanism offers a potential explanation for cue-induced craving and relapse to cocaine use.
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