Category Archives: Receptors in the CNS

Dopamine: Helps you Pick Up Chicks

Disclaimer:  There’s a  bit of brain lingo here.  If you and the ‘matter are cool, by all means, keep on keepin’ on.  If words like pontomesencephalotegmental complex freak you out, however, might I suggest this fun neuroanatomy review?

Image

Oh, don’t sigh.  You know you like it.

Dopamine is a neurotransmitter synthesized in your brain from an essential amino acid called tyrosine.  You get much of your body’s tyrosine from your diet, notably from high-protein foods like cheeses, turkey, and pumpkin seeds.

But…why are we talking about dopamine?  Since it is one of our more prominent CNS neurotransmitters, dopamine is implicated in tons of neurological and psychiatric disorders.  Researchers toil every day to put their paws on what exactly dopamine is doing in the brain and spinal cord.  So I am sure all of them will appreciate me narrowing down thirty years of hard work into a very brief introduction to this complex and fabulous neurotransmitter, and the receptors it affects.

There are actually quite a few ways that dopamine helps you pick up baby chickens.

1) It helps you concentrate on something you want to do, like scooping up a yellow fluffball of joy.

2) It helps you recognize that picking up something fluffy is going to make you feel good.

3) It helps you control your movements so you gently pick up the baby fluffball instead of crushing it between your ruthless human paws.

4) It helps bring joy into your heart when you pick up that little baby chicken and it peeps at you.

5) It helps you remember that you might get some chick pee (bahaha!) on your hands, so you bring some hand sanitizer.

Anyway, as of NOW, we know dopamine follows a few different pathways in the brain. These tracts are lined with dopamine receptors D1 and D2 (and D3-5 but for now let me explain what I “know”, which does not include much about the other ones.  Enlighten me, I beg you.). The densities of these G-protein coupled receptors vary by location, which probably determines their varied actions.  Two very important receptor pathways are the mesolimbic/mesocortical tract and the nigrostriatal pathway.

Dopamine Pathways. In the brain, dopamine play...
(Photo credit: Wikipedia)

The mesolimbic/mesocortical tract originates in dopaminergic neuronal bodies in the ventral tegmental area of the brain.  As you may have observed from its name, it is actually two different tracts, but for now let’s just treat it as one.  It feeds dopamine to the limbic system and cerebral cortex and is often referred to as the “reward pathway”.  We use rewards (thank you Pavlov!) not only to learn how to get what we want, but to be able to recognize things that are harmful to us.  Much research has been devoted to the role of dopamine in addictive behaviors.  Additionally, an imbalance of dopamine in this pathway (especially in the prefrontal cortex) is one of the major prevailing theories of schizophrenia.

The nigrostriatal pathway originates in dopaminergic neurons in the substantia nigra. This pathway is important because it feeds dopamine to the striatum of the basal ganglia–a dense gathering of neurons that are responsible for learned automatic movements, like walking up stairs and feeding yourself.  Too little dopamine (or dopamine receptors) in this pathway can cause a disrupt in the extrapyramidal tract of motor neurons in your spinal cord.  The result is the rigidity and spasticity seen in Parkinson’s Disease.

*If you did not click on the links as you were reading, I urge you to do so for your own well-being.

GABA GABA GABA!

Ball-and-stick model of the gamma-aminobutyric...
Ball-and-stick model of the gamma-aminobutyric acid (GABA) molecule. (Photo credit: Wikipedia)

Why say it three times?  Because if you really try, you can attribute almost ANYTHING your body does to GABA (it might take a little creativity, but work with me here).  It is a neurotransmitter with a receptor by the same name (If you are feeling cheated because no one was creative enough to make the name of the receptor more interesting, don’t fret. The people who name genes and chemical compounds have gone a little overboard).  GABA (gamma-aminobutyric acid) receptors are mostly in the CNS, and they are responsible for managing neuronal action potentials that control everything from the sleep-wake cycle to memory.

For now, we will focus on the GABA-A (I just call them GABAAAAAAAH, but I’m not positive that is a generally accepted pronunciation) receptors, the hypothesized focus of a group of drugs known as anxiolytics, amnesics, and sedative hypnotics.

GABA-A receptors are a special type of ligand-gated chloride channel, and one of their particularly special functions is that they are inhibitory to neurons.  That is, the influx of Cl- that they allow causes hyperpolarization, which reduces the possibility of an action potential.  So if, say, you are having some issues with overactive neurons (like epilepsy), GABA-A agonists might be prescribed to calm those suckers down.

The other cool thing about GABA receptors is that, although their main ligand is GABA (and a few other compounds), they have all of these little ports called allosteric sites.  Allosteric binding results in potentiation or inhibition of a receptor.  In the case of GABA-A, potentiating allosteric sites can be bound by many of the drugs in the sedative hypnotic and antiepileptic classes, including benzodiazepines, barbituates, and vodka (well, alcohol).

Potentiation (agonism) of the GABA-A receptor has lots of useful actions.  In anesthesia, it is used to make you sleepy and calm, to prevent nausea, and to help you forget much of what just happened to you (hallelujah!).  In psychiatry, GABA-A potentiation is useful for temporarily reducing severe anxiety.  In general medicine, GABA agonists are used to prevent seizures, stop status epilepticus (uncontrolled, continuous seizures), and as a sleep aid. As you can imagine, GABA antagonism results in quite the opposite reaction:  increased neuronal activity and wakefulness.