A research team investigating the mechanisms underlying general anesthesia finds that stimulating a specific group of neurons in mice produces signs of arousal -- including getting on their feet and walking -- even as the animals continue to receive the anesthetic drug isoflurane. In addition to developing ways to actively reverse anesthetic-induced unconsciousness, the findings may someday help improve treatment of conditions such as coma or opioid overdose.

The current study used optogenetics, a method of activating specific populations of neurons by means of light, to target only dopamine-responsive neurons in the VTA. Every one of six mice engineered to express a light-responsive protein in dopamine neurons showed signs of arousal -- including moving, standing up and walking -- in response to pulses of light delivered to the VTA, even while they continued to receive isoflurane.

Use of an agent that blocks signaling by the D1 receptor -- one of five dopamine receptors -- prevented the arousal response to light stimulation, indicated that dopamine signaling was responsible for counteracting anesthetic effects. EEG readings taken during optogenetic stimulation of the VTA showed patterns similar but not identical to those of unanesthetized animals.

The report published in the journal Proceedings of the National Academy of Sciences.

"We now need to study whether the activation of dopamine neurons can help in coma-like states," says the lead author. "One of the effects of dopamine neuron stimulation we observed was increased respiratory rate, which may have implications for treating the sedating effects of medications such as opioids and provide insight into how to save the lives of more overdose patients."

http://www.pnas.org/content/early/2016/10/18/1614340113