Posts Tagged ‘ dopamine

Dopamine

Dopamine (DA) is a neurotransmitter present in many animals, from the honeybee to the dolphin. It is involved in many behaviors associated with motivation and reward. The majority of dopamine in humans is released from two areas.

First is the the substantia nigra, whose darkly pigmented cell bodies supply dopamine to the deep motoric nuclei of the basal ganglia. Dopamine concentrations in one nuclei, the putamen, exceed anywhere else in the brain reaching a level of 5740 nanograms per gram. Dopamine released in this nigrostriatal pathway helps us quickly execute our motor patterns and associated movements. For instance, if dopamine drops to very low levels on one side of this system Parkinsonian symptoms will arise, with sluggish arm and leg movements on one side of the body.

Second is the ventral tegmental system. Its cells send much of their dopamine up to the nucleus accumbens in the ventral striatum, and a separate pathway supplies the limbic system. Two other branches supply dopamine to the cortex in the prefrontal and cingulate regions. An especially dense network of dopamine fibers covers the inner part of the prefrontal lobe, the same region where the thalamus sends its major input. The intersection of these two pathways in the prefrontal cortex remains one of the brain’s most constant features, dating back to the tree shrew and reminding us of our origins in the forest.

Suppose you take a rat, normally a social animal, and reduce its social stimuli over a prolonged period making it a hermit in a cage. The different dopamine systems react in different ways – the metabolic activity of the dopamine cells supplying the frontal lobes slows, whereas metabolism increases in dopamine cells projecting up to the dorsal and ventral striatum. Even though the isolated rats have now quieted down and show few spontaneous behaviors (frontal lobes), they jump more when an electrical shock is delivered to the foot (dorsal and ventral striatum). Increased social exposure causes a reversal of these effects – more active and less nervous rats.

Each person’s brain is unique, as the number and distribution of dopamine receptors varies widely. Early in life, brain development responds to male or female hormones present. Male rats already show more evidence of dopamine receptors in their cortex and amygdala only a few days after being born.

There are five known dopamine subreceptors in humans. The most abundant dopamine subreceptor in the nervous system is the D1 receptor, which regulate neuronal growth and development and mediates some behavioral responses. It also stimulates adenylyl cyclase and activates cyclic AMP-dependent protein kinases, involved in the regulation of glycogen, sugar, and lipid metabolism. D2 receptors are gaining prominence as potential keys to certain diseases, as increased D2 receptor levels have been linked to schizophrenia, certain Parkinson’s symptoms, and narcolepsy.

The major functional role of dopamine systems in the human brain appears twofold. First, there are prominent motoric effects. Decades of research on rats and mice have shown that any cause of indirect release of dopamine into the nucleus accumbens causes rats to engage in specific motor sequences: they move around more, they sniff more, and engage in repetitive grooming behaviors. This is not unlike a human who has experienced dopamine increase caused by cocaine or other drug consumption, as they fidget, sniff and lick their lips, run their fingers through their hair, or pick at the skin.

But there is more than just a general mobilizing or energizing effect. This became clear when experiments were undertaken as animals pressed on a lever, working to receive food as a reward. Drugs which increased dopamine levels caused the animals to become more selective and efficient, suggesting that dopamine helps to sustain goal directed behavior. While dopamine was initially dubbed the “pleasure” neurotransmitter, recent research suggests that pleasure is a less appropriate term than “motivation”. As any speed freak will tell you, after a certain point self-administration of the drug becomes distinctly dysphoric, but the desire to continue dosing remains strong and is not correlated with the level of
“pleasure” (if any) that the next dose will produce.

There are also interesting correlations to personality. “Extroverted” personalities tend to show higher spinal fluid levels of dopamine breakdown products, and a set of aggressive patients also showed the same evidence of higher dopamine turnover. After practicing yoga meditation for six months however, the levels of dopamine breakdown products of the aggressive patients fell from an average of 51 nanograms per liter to 41 nanograms per liter.

The Three Biogenic Amine Systems

The three potent neurotransmitters dopamine, norepinephrine, and serotonin were known to science prior to the 1960s, but the precise structure and extent of their nerve cells was unclear. Annica Dahlström and Kjell Fuxe used the novel technique of histoflourescence to map the pathways that released them into the brain in a landmark paper in 1964, “Evidence for the existence of monoamine neurons in the central nervous system“. The field exploded, and strange facts emerged. They are greatly outnumbered, as our brain only holds a million or so of them. But they exert a huge influence over the remaining billions of other nerve cells, fanning out into up to 500,000 nerve endings connecting to hundreds of other distant cells.