From Mouse to Man

What the latest basic science research is telling us about the human mind

What is dopamine?

The neurotransmitter's role in the brain and behavior.

What is dopamine? What does it do and how does it do it? These questions have caused controversy in neuroscience for decades. A new study from the UK may have some of the answers.

The word dopamine means very different things to different people, from drug addiction to Parkinsons disease to a Hollywood movie dopamine is part of mainstream culture as well as an enduringly fascinating research topic in neuroscience. It has been part of over 110,000 research papers in the last 60 years but is still a source of controversy among neuroscientists. Attempting to sum up the function of dopamine in a brief blog post is not going to be easy. I am going to leave many research scientists dissatisfied and some downright angry!

Lets start with the basics. Dopamine is a neurotransmitter, one of those chemicals that is responsible for transmitting signals in between the nerve cells (neurons) of the brain. Very few neurons actually make dopamine. Some, in a part of the brain called the substantia nigra, are the cells that die during Parkinsons disease. The functions of others, located in a part of the brain called the ventral tegmental area (VTA), are less well defined and are the major source of the aforementioned controversy (and the focus of this post). When dopamine neurons become activated, they release dopamine.

One of the best described roles for VTA dopamine neurons is in learning about rewards. VTA dopamine neurons become activated when something good happens unexpectedly, such as the sudden availability of food. Most abused drugs cause the release of dopamine and this is thought to contribute to their addictive properties.

But what about bad things? Do they activate dopamine neurons? It's perhaps even more important to learn when something bad is going to happen than something good; with predators or disease you often don't get a second chance. Is dopamine involved in learning about bad things? Herein lies some of the controversy surrounding dopamine. Not all the neurons in the VTA make dopamine. Many studies had suggested that the sudden presentation of aversive or noxious stimuli such as pain caused the activation of some neurons in the ventral tegmental area, but were these dopamine neurons?

In 2004 Mark Ungless and colleagues at the University of Oxford (UK) published a paper in the journal Science indicating that dopamine neurons were universally inhibited by aversive events. They used a painstakingly detailed approach to identify those neurons which were activated or inhibited by aversive stimuli and then biochemically analysed those neurons to determine if they truly were dopamine neurons. They did find that some neurons became activated by aversive stimuli, but these neurons did not make dopamine.

The findings were very clear but were controversial. They did not sit well with other studies on the role of dopamine, including some which showed that treatment with drugs which block the action of dopamine could block learning about aversive events. Also, chemical measurements indicated that dopamine was released by animals undergoing a stressful experience. If dopamine neurons are not activated when learning about aversive events, how is this dopamine being released? and why would blocking the effects of dopamine prevent learning about aversive events?

Ungless and co, now at the UK Medical Science Research Council, Imperial College, London, hypothesized that the devil may be in the detail; maybe the VTA isn't a single, uniform part of the brain but is composed of functionally different subregions. Before conducting their latest study, published in the Proceedings of the National Academy of Sciences (USA) they went back and looked again at the literature about dopamine neurons in the ventral tegmental area. They observed an experimental quirk; most studies of VTA dopamine neurons, those showing that dopamine neurons aren't activated by aversive stimuli, were measuring responses from a same small part of the VTA, called the dorsal VTA. What if neurons in a different part of the VTA became activated by aversive stimuli and released dopamine?

To test this, they gave rats an electric shock (not an electrocution, just a moderate electric shock, much the same as a dog would receive from a shock raining collar). During this electric shock, they recorded the activity of neurons from the dorsal VTA and a slightly different part of the VTA called the ventral VTA. They found, like others had previously, that neurons in the dorsal VTA were either inhibited by an aversive stimulus or did not respond at all. In contrast, those neurons in the ventral VTA became activated by the footshock. In fact, they became very activated, exhibiting a type of response known as "burst firing" that would be expected to produce a profound dopamine release.

So, that would appear to be that, problem solved! But there was another twist. As I wrote earlier, one of dopamine's best known roles is in learning about rewards. Relief from an aversive event can be considered as a reward. The pattern of learning exhibited by animals and humans is similar when comparing a "real" reward (e.g, food) or relief from an aversive stimulus (e.g; when an electric shock is turned off). What Ungless and co. observed was that those neurons in the dorsal VTA, those which were unresponsive or were inhibited by the electric shock, those neurons became transiently activated when the shock was turned off. This would be consistent with their role in reward learning while also partially explaining why dopamine blockers impair learning about aversive events.

So, the story of dopamine has evolved a little but further while becoming a little but more complicated; not all parts of the ventral tegmental area are the same!

 

Philip M. Newton, Ph.D. is a Neuroscience Lecturer at Swansea University Medical School in the United Kingdom.

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