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

Elife. 2015 Jul 24;4:e09275. doi: 10.7554/eLife.09275.

Abstract

One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.

Keywords: GABA neurons; GABAB receptors; dopamine neurons; glutamate release; morphine; mouse; neuroscience; rat; ventral tegmental area.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopaminergic Neurons / drug effects*
  • Glutamic Acid / metabolism*
  • Male
  • Morphine / metabolism*
  • Narcotics / metabolism*
  • Presynaptic Terminals / drug effects*
  • Rats, Sprague-Dawley
  • Ventral Tegmental Area / drug effects*

Substances

  • Narcotics
  • Glutamic Acid
  • Morphine

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.