Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation

15 figures

Figures

Identification of VTA-DA neurons in rats.

(A) Electrophysiological properties of VTA-DA neurons. Left panel: representative traces showing a large hyperpolarization-activated current (Ih) in whole-cell voltage-clamp recording. Holding …

https://doi.org/10.7554/eLife.09275.003
Effect of morphine on spontaneous firing of VTA-DA neurons in rats and the influence of the NMDA receptor antagonist APV and the AMPA receptor antagonist DNQX on the effect of morphine on spontaneous firing of VTA-DA neurons in rats.

(A) Effect of morphine on spontaneous firing of VTA-DA neurons. Left panel: representative spontaneous firing traces before and after morphine (10 μM). Middle panel: time course of spontaneous …

https://doi.org/10.7554/eLife.09275.004
Effects of morphine on the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and paired pulse facilitation (PPF) of VTA-DA neurons in rats.

(A) Effects of morphine on the frequency of sEPSCs in the presence of extracellularly applied picrotoxin (PTX) in VTA-DA neurons. Left panel: typical current traces of sEPSCs before and after …

https://doi.org/10.7554/eLife.09275.005
Effects of morphine on glutamate release from the ventral tegmental area (VTA) synaptosomes of rats and the frequency of sEPSCs in mechanically dissociated VTA-DA neurons from rats.

(A) Effects of morphine on glutamate release from VTA synaptosomes. Average concentration of glutamate release before and after application of morphine (10 μM) from VTA synaptosomes (n = 6 samples …

https://doi.org/10.7554/eLife.09275.006
Effect of exogenous application of GABA and 470 nm light stimulation on the frequency of sEPSCs in the presence of intracellularly applied PTX in VTA-DA neurons.

(A) Effect of exogenous application of GABA on the frequency of sEPSCs of VTA-DA neurons in rats. Left panel: typical current traces of sEPSCs before and after GABA (10 μM) in the presence of …

https://doi.org/10.7554/eLife.09275.007
Influence of the GABAA receptor antagonist PTX and the GABAB receptor antagonist CGP54626 on the effect of exogenous application of GABA as well as the influence of the GABAB receptor antagonist CGP54626 on 470 nm light-induced inhibition of the frequency of sEPSCs in VTA-DA neurons.

(A) Influence of the GABAA receptor antagonist PTX on the effect of exogenous application of GABA of VTA-DA neurons in rats. Left panel: typical current traces of sEPSC before and after GABA (10 μM) …

https://doi.org/10.7554/eLife.09275.008
The presence of GABAB receptors in the presynaptic glutamatergic terminals of the ventral tegmental area (VTA) in rats.

(A) GABAB receptor expression in the synaptosomes from the VTA. A representative Western blot shows GABAB receptor expression in the synaptosomes from the VTA. (B) GABAB receptor expression in the …

https://doi.org/10.7554/eLife.09275.009
Effect of the GABAB receptor antagonist CGP54626 and the GABAA receptor antagonist PTX on the frequency of sEPSCs of VTA-DA neurons in rats.

(A) Effect of the GABAB receptor antagonist CGP54626 on the frequency of sEPSCs in VTA-DA neurons. Left panel: typical current traces of sEPSCs before and after CGP54626 (2 μM). Middle panel: …

https://doi.org/10.7554/eLife.09275.010
Effect of 590 nm light stimulation on the frequency of sEPSCs and influence of light-induced disinhibition of glutamatergic input and the GABAB receptor antagonist CGP54626 on the effect of morphine on the frequency of sEPSCs in VTA-DA neurons.

(A) Effect of 590 nm light stimulation on the frequency of sEPSCs of VTA-DA neurons in mice. Left panel: 590 nm light inhibits current injection-induced firing of action potentials in VTA GABA …

https://doi.org/10.7554/eLife.09275.011
Effect of the selective presynaptic GABAB receptor antagonist CGP36216 on spontaneous firing and the influence of the selective presynaptic GABAB receptor antagonist CGP36216 on the effect of morphine on spontaneous firing of VTA-DA neurons in rats.

(A) Effect of the selective presynaptic GABAB receptor antagonist CGP36216 on spontaneous firing in VTA-DA neurons. Left panel: representative spontaneous firing traces before and after CGP36216 …

https://doi.org/10.7554/eLife.09275.012
Influence of intra-ventral tegmental area (VTA) injection of the presynaptic GABAB receptor antagonist CGP36216 on morphine-induced increase in locomotor activity in rats.

(A) Injection sites were verified under light microscope. Left panel: Representative Nissl-stained photomicrograph of cannula tracts terminating in the VTA. Right panel: location of the injection …

https://doi.org/10.7554/eLife.09275.013
Influence of intra-ventral tegmental area (VTA) injection of the presynaptic GABAB receptor antagonist CGP36216 on intra-VTA injected morphine-induced conditioned place preference (CPP) in rats.

(A) Schematic representations of injection cannula tips in the VTA of rats used in data analyses. Numbers indicate coordinates relative to bregma. (B) A schematic of the experimental design for CPP …

https://doi.org/10.7554/eLife.09275.014
Author response image 1
Effect of GABA on the frequency of sEPSCs and the influence of GABAB receptor antagonist CGP54626 on the effect of GABA on the frequency of sEPSCs in VTA-DA neurons of mice.

(A) Effect of GABA on the frequency of sEPSCs in VTA-DA neurons. Left panel: Typical current traces of sEPSC before and after GABA (10 μM). Middle panel: Time course of the frequency of sEPSCs …

https://doi.org/10.7554/eLife.09275.017
Author response image 2
Effect of GABAB receptor antagonist CGP54626 on the frequency of sEPSCs and its influence of on the effect of morphine on the frequency of sEPSCs in VTA-DA neurons of mice.

(A) Effect of GABAB receptor antagonist CGP54626 on the frequency of sEPSCs in VTA-DA neurons. Left panel: Typical current traces of sEPSC before and after CGP54626 (2 μM). Middle panel: Time course …

https://doi.org/10.7554/eLife.09275.018
Author response image 3
Influence of selective presynaptic GABAB receptor antagonist CGP36216 on the effect of morphine on the firing in VTA-DA neurons of mice.

(A) Representative spontaneous firing traces recorded before and after morphine (10 μM) in the presence of CGP36216 (100 μM). (B) Time course of spontaneous firing before and after morphine in the …

https://doi.org/10.7554/eLife.09275.019

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