Symbols of addiction – Part 2

Addiction is always irrational – and one little story about irrationality involves a man who turns in exasperation to his girlfriend one day and says, “You’re like the square root of 2.” Puzzled, she asks, “Why?” And he replies, “Because you’re completely irrational.” If you don’t get it, then I won’t bore you further with an explanation – but you might like to search for “irrational numbers” if you’re curious.

The brain pathways

Back to addiction: Although psychological factors often have a bearing on many forms of addiction, there is also a chemical basis for practically all forms of addictive behaviour. It is a very interesting story how the body succumbs to addiction – and it starts with the dopaminergic pathways in the brain. These are neural pathways which shift a neurotransmitter called dopamine around various regions of the brain – the pathways most commonly associated with addiction are the mesolimbic pathway, the nigrostriatal pathway, and to a lesser degree, the mesocortical pathway.

As an aside, dopamine is also involved in the tuberoinfundibular pathway – and problems with this pathway are associated with hyperprolactinaemia, a condition which affects menstruation in women and sexual dysfunction in men, among other things. As explaining each pathway would involve long discourses into the neurobiology of the brain, we will restrict ourselves to only discussing elements mainly involved with the mesolimbic pathway (MLP), which probably drives the most common forms of addictive behaviour.

The MLP is often referred to as the Reward Pathway for this brain pathway directly influences the fuzzy, warm, pleasant responses we feel when something satisfies our urges. As such, the MLP is a crucial component of what motivates and incentivise us to follow our goals. Why nature has developed a system of controlling behaviour via a rewards system is actually very interesting because of its general efficiency, unless of course, it becomes a detrimental syndrome – more on this a little later.

The MLP is located right in the middle of the brain and it connects the Ventral Tegmental Area (VTA) to the Nucleus Accumbens (NAc), via a series of complex connections that also involves the hypothalamus, amygdala and hippocampus. There are also some interactions with the main frontal cortex, the dorsal raphe, the locus coeruleus and significantly, the amygdala – don’t worry, all will be clear (or at least, clearer) in a little while.

Locations of VTA and NAc in the human brain.

Note that the use of dopamine pathways is not a new development and it is certainly not exclusive to humans or even mammals – based on research on fossils many millions of years older than mammals, it was found that dopamine-activated neurons had been controlling behavioural responses in primitive worms and insects even then. As it is such a primitive, compelling piece of circuitry in the brain, the dopamine pathways probably also affect some of the other primal responses in humans, such as lust, jealousy, revenge and greed.

The main chemicals in focus in the MLP are dopamine, gamma-aminobutyric acid (GABA) and a curious amino acid called glutamic acid (often presented as glutamate, where a mineral ion is attached; eg. monosodium glutamate). Dopamine is synthesised from phenylalanine or tyrosine, which are amino acids found in proteins – if present, phenylalanine is converted into tyrosine via the enzyme phenylalanine hydroxylase and tyrosine is next converted into levodopa (L-dopa) by the action of the enzyme tyrosine hydroxylase.

L-dopa is then converted into dopamine by a versatile enzyme called aromatic L-amino acid decarboxylase (AADC) via a process called decarboxylation, which can be summarised as the removal of a COOH molecular sequence from a target compound. Note that these series of reactions will become more significant later on when discussing noradrenaline and the amygdala. The participation of glutamate is interesting: it can act as a neurotransmitter in its own right or it can involve a glutamate enzyme which acts as a precursor for the synthesis of GABA from glutamate, leaving some CO2 (carbon dioxide) as a residue – this reaction is catalysed by glutamic acid decarboxylase (GAD) which appears to be expressed solely by those neurons that reacts to GABA.

Our addiction to beer and coffee and other stuff has a psychological basis but there is also a chemical basis for practically all forms of addictive behaviour.

As an aside, GAD is also produced in the pancreas and it has been observed that people with Type 1 diabetes also tend to have antibodies against GAD – these antibodies disrupt the function of the pancreas and hence interfere with the production of insulin.

And regarding glutamates, the glutamates we get from food normally cannot cross the Blood-Brain Barrier so that feeling of drowsiness from eating too much savoury food cannot be attributed to the effect of food glutamate on the brain – the tiredness after overeating is simply due to gluttony overloading the digestive system. The brain isn’t that simple as there are other compounds which interact directly or indirectly with the MLP, such as noradrenaline, serotonin, anandamide, various endogenous opioid neuropeptides (collectively known as endorphins) and so on – the full list is quite extensive and still quite possibly incomplete as it stands today.

In case you’re wondering how the brain can produce these chemicals so quickly, the answer is that certain amounts of several neurotransmitters are actually manufactured in advance, then transported by a protein called the vesicular monoamine transporter (VMAT) for storage in the synaptic vesicles near the synapses, ready for instant use. Once the vesicles are depleted, the brain produces more neurotransmitters as required to keep the required reaction going.

Why the brain uses rewards

What is rather fascinating and also somewhat infuriating about the brain is that we know much more about how it works rather than why it works the way it does. For example, there is a good theory about how the use of rewards is much more efficient than the alternative, which would require the brain to store all responses to all the foods we have ever eaten – the good foods would get good scores and the bad foods would get bad scores.

If we did not have a reward system, it would mean that every new food we come across has to be evaluated, digested and scored – if the food is poisonous, then life would end there and then and we would not be able to prevent the poisoning because we would have had no previous experience of the poison. But by having a reward system which makes us “feel good” or “feel bad” in some fuzzy way about new food substances, probably based on foods with analogous tastes, then the brain simplifies hugely the whole process of determining between good or bad without having to go through a huge list of previous encounters.

Sweet and fatty foods ‘taste good’ and bitter and sour stuff simply ‘taste bad’ – and this ability to generally distinguish between good and bad food using ‘fuzzy logic’ significantly enhanced many species’ chances of survival. Photo: The Star

sweet and fatty foods “taste good” and bitter and sour stuff simply “taste bad” – and this ability to generally distinguish between good and bad food using “fuzzy logic” significantly enhanced many species’ chances of survival

So in general, sweet and fatty foods “taste good” and bitter and sour stuff simply “taste bad” – and this ability to generally distinguish between good and bad food using “fuzzy logic” significantly enhanced many species’ chances of survival, including our own. Of course, this reward system also applies to behaviours other than eating – whether it is the comfort of finding shelter from inclement weather, or the pride of a hunting success, or perhaps the vindication of killing an enemy. Rewards do not always end with positive results for everyone involved.

That is currently the best theory about why we have a reward system in our brains – and it is quite a compelling doctrine called the Anhedonia Hypothesis (AH) devised by Roy Wise in 1982 which directly links dopamine with behaviours driven by rewards – and such behaviours can lead to addictions further down the line. But in truth, the function of dopamine isn’t exactly so simple and straightforward either – else it wouldn’t be so interesting. For one, although the VTA produces and sends dopamine to the NAc as a stimulatory, positive response to a food substance which is attractive and pleasurable, the levels of dopamine actually drop after extended exposure to the same food – in short, the sense of a worthy reward fades over time.

This is why food cravings die off after some time, else we would be compelled to eat the same foods every single day – a classic subjective example may be sushi, which can be seriously enjoyed several times in a row but after that, some other kinds of hot food suddenly become more desirable. There may be an evolutionary basis for why dopamine levels change like this – it might be a signal to diversify and consume different foods so as to maximise the nutritional intake.

Glutamate in the brain is an excitatory chemical causing the brain neurons to fire and become more receptive to other neurotransmitters during any brain activity – and its action can sometimes be akin to setting off a chain of fireworks. Therefore, the actions of glutamate (and other neurotransmitters) have to be modulated to prevent over-activity and this regulation is done by GABA, which damps down and controls the signalling between brain neurons. As mentioned earlier, GABA is produced by the neurons themselves when glutamate is catalysed by GAD and this appears to be a self-moderating function in neural signalling.

As an aside, it has been shown that glutamate is actually toxic, more specifically it is an excitotoxin – too much glutamate in the brain causes excitotoxicity which results in brain cell death via a process called apoptosis, which might be a glorified term to describe the suicide of brain cells after having too much stimulation.

Many people are addicted to Ipoh’s famous ‘mixed rice’ at the Yong Suan coffee shop on Jalan Kalsom, here complete with ayam merah, fish roe curry, sotong curry, coconut sambal, salted egg and a secret gravy. Photo: The Star

However, from the story so far, it seems unlikely that any food addictive behaviour can come about purely as a result of dopamine – even after being initially thrilled and immensely rewarded by interesting foods, the brain damps down by itself the production of dopamine after any extended exposure to the foods and GABA moderates the neural excitement promoted by glutamate. The theory therefore is that addictive behaviour arises from the interplay of other factors which interact with the MLP, and some of these factors may be rather surprising, though always interesting – and it isn’t always what you might assume.

It reminds me of a little story about an old man who visits a doctor with his wife for his medical examination. After looking over the old gentleman, the doctor tells him, “I need to take some samples of your stools, urine and blood.” The old man leans over, hard of hearing, and asks, “What?” So the doctor repeats more loudly, “I need samples of your stools, urine and blood now.” The old man asks again, “What did you just say?”

At this point, the wife gets up and shouts in his ear, “The doctor wants your underwear!”

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Next: The chemistry of addictive behaviour – the later years

Source : Star2.com