Dopamine is one of the few neurotransmitters that most people have probably heard of. It’s the ‘reward chemical’, the one that makes us feel good when we reach a goal or do something we enjoy, right? Well, it’s a bit more complicated than that. Okay, a lot more complicated.
While dopamine does have a lot to do with pleasure and reward, it has many other effects depending on where in the brain we’re releasing it and what receptors it’s binding to. It’s involved in attention, hormones, and motor control, and its dysfunction is part of conditions from schizophrenia to Parkinson’s disease.
In the article “Beyond cAMP: the regulation of Akt and GSK3 by Dopamine Receptors”, the authors take a look at D2 dopamine receptors and how they affect a signaling pathway called the Akt/GSK3 pathway in the hopes that it might give a better idea of how to deal with dopamine-related conditions. This pathway is especially important for that work because among other things, it affects the entire outlook of the cell- how it will do its job, whether it needs to move, or replicate, or self-destruct. When dopamine binds to D2 receptors, they inhibit Akt, and Akt normally inhibits GSK3, that means GSK3 can go to work.
This is important to treating dopamine conditions because the drugs we have now are kind of like hammers when we need tweezers. For example, in bipolar disorder and schizophrenia, when dopamine has too much of an effect, we inhibit dopamine, and in Parkinson’s, when there’s too little dopamine signaling going on, we add more dopamine. Sounds easy enough, but remember the part about dopamine doing a lot of stuff? Unfortunately when there’s a problem it’s usually not with all of it. There’s too little or too much in a specific area of the brain, and when we try to act too broadly we can sort of fix the local problem, but globally we’re causing nasty side effects. Luckily research into the Akt/GSK3 pathway has given us some better targets to shoot for. For example, people with schizophrenia have too much dopamine *signaling*, but it’s not really dopamine’s fault. They have too little Akt, which means dopamine can overpower it too easily. So drugs targeting Akt instead of dopamine should fix the problem without mucking everything else up. Hopefully in the near future, this research will bear fruit in the form of ‘tweezers’—medication that does what we want, and nothing else.
