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BDNF-dependent synaptic sensitization in midbrain dopamine neurons after cocaine withdrawal

Abstract

The neural mechanism underlying the relapse to drug use after drug withdrawal is largely unknown. We found that after withdrawal from repeated cocaine exposure, excitatory synapses onto dopamine neurons in the ventral tegmental area (VTA) of the rat midbrain became highly susceptible to potentiation by weak presynaptic stimuli, an effect requiring endogenous brain-derived neurotrophic factor–tyrosine kinase B (BDNF-TrkB) signaling. The elevated BDNF expression in the VTA after cocaine withdrawal may prime these synapses for potentiation by cue-associated activity, triggering drug craving and relapse.

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Figure 1: Synaptic potentiation in VTA dopamine neurons induced by a train of weak presynaptic stimulation (WPS) in rat midbrain slices.
Figure 2: Exogenous BDNF facilitates activity-induced synaptic potentiation in dopamine neurons.
Figure 3: Mechanisms underlying WPS-induced synaptic potentiation.

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Acknowledgements

We thank C.C. Lien, J.L. Du, Z.R. Wang and L. Cancedda for critical comments and suggestions. This work was supported by grants from the US National Institutes of Health.

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Correspondence to Mu-ming Poo.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Electrophysiological identification of dopamine neurons. (PDF 357 kb)

Supplementary Fig. 2

Enhanced LTP in rats examined 10-15 d after cocaine withdrawal. (PDF 117 kb)

Supplementary Fig. 3

Bath perfusion of BDNF sensitized the excitatory synapses on dopamine neurons for synaptic potentiation by weak presynaptic stimulation (WPS). (PDF 79 kb)

Supplementary Methods (PDF 91 kb)

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Pu, L., Liu, Qs. & Poo, Mm. BDNF-dependent synaptic sensitization in midbrain dopamine neurons after cocaine withdrawal. Nat Neurosci 9, 605–607 (2006). https://doi.org/10.1038/nn1687

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