Biochemistry 10

the chemistry of plèasure

plèasure is what we learn it to be!

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Until 1998, the common conception was that plèasure, as the opposite of pain, was a reward mechanism that motivated humans and probably all animals.  (Pain provided the mechanism of avoidance.  But it was realized that pain isn't an effective way to teach avoidance.)  The plèasure could come in a variety of ways from pleasant experiences such as tasty food, supportive companions, imagined experiences, or even from successfully sacrificing for the good of others. It might also originate from a remembered dream.   Our human experiences suggested that plèasure usually derives from a conscious awareness of pleasant sensations.  (We don't seem to get much plèasure from circumstances we are unaware.)  And if we are distracted from a plèasurable experience, we might also loose a sense of plèasure much the same as pain can sometimes be reduced by distracting away one's attention.  Having experienced such plèasure, a person would be motivated to extend or repeat the experience.  Thus plèasure (sometimes called a reward) was thought important to learning.

It may be worth noting that sometimes a small twist in our paradigm is closer to reality.  While there has long been suspicion that there is a close connection between plèasure and pain, there has always been evidence that pain and plèasure are not the two extremes of a single continuum.  Sensing pain has the characteristics of being a built in alarm of our nervous system, while plèasure has the varied characteristics of being learned.  (For example, we don't all enjoy eating the same foods.)  But the key 1998 observation was that the molecule which had been associatiated with plèasure, dopamine, was found to be released BEFORE the plèasurable event rather than afterwards as the previously presumed mechanism required!  So instead of being the chemical reward for the brain, dopamine is more likely part of a mechanism to draw our conscious attention to an event of importance based on prior learning.  Such an event could either lead to the satisfaction of a need, be associated with satisfaction of a need, the avoidance of some pain, or even the thrill of experiencing a pain.

Consciousness remains poorly understood.  (See more on that in Consciousness) That lack of understanding of consciousness also impairs our understanding of plèasure.  The development of plèasurable habits, emotions (such as the facial expression of liking a taste), and motivations occur in various parts of the brain and involve several chemical mechanisms which are also not fully understood.  In short, there is much to be determined about plèasure and it relationship with learning.

But there is much evidence of the importance of plèasure for human beings.  Experiences most people find plèasurable, from enjoying eating and drinking to witnessing a sunset or remembering a pleasant event, help reinforce activities which makes life more likely to succeed.  While many people share common forms of plèasure, there are people who do no find one of more of those plèasurable.  Food or music which generally give plèasure in one culture or generation, may not provide plèasure in a different culture or generation.  This suggest that perhaps plèasure is what we learn it to be.  Particular plèasures are not innate, governed by our genes, but rather somehow learned.

If that is the case, then a major questions is how do we learn what activities and experiences provide us plèasure?  This is a particularly tough question because many people take plèasure at helping others, even when that requires some degree of self-sacrifice.  And some people even find plèasure while experiencing pain and discomfort, such as in strenuous exercise and pushing the limitations of their bodies in contests and games.  How can we learn things which don't have intrinsic positive rewards but punishments and do not seem in our immediate best interests?  Knowing at least some of the mechanisms which occur inside and between nerves in the brain, it seems plausible that all forms of plèasure originate by association with our basic survival needs.  And those may extend back to our first sensations when our nervous systems where developing before and shortly after birth.  What follows is a tentative proposal of how that might occur.

Plèasure Mechanism

There is not a single location for plèasure in the body.  A diverse system of sense organs, signal transmitting nerves, and processing and recording in the brain are involved:

  1. More than a half dozen distinguishable types of nerve detectors comprise our sense organs.  In each, very similar molecules and membrane organizations function as triggers for initiating electrical signals carrying information (as detailed in Touch & Hearing, Tasting & Smelling, Pain, Sight & Color).  These nerve receptors are exclusively the only external ways to initiate plèasure.  We can learn nothing except as the result of signals they generate.

  2. The electrical signals are transmitted along the surface of the nerve fiber by chemical reactions releasing flows of ions and small molecules.  While these signals involve a spike in electrical voltage, they are only vaguely similar to the flow of electrical signals carried by metallic wires.  (Nerve Messaging)

  3. In the retina of the eyes and olfactory bulb above the nose and other locations, collections of nerves pre-process the signals for commonality, differences, persistence, change and possibly other patterns.  (Contact by Nerve)

  4. At a junction between nerve cells (synapse), chemical reactions and a flow of excreted molecules and ions transport the signal accross the gap.

  5. In the brain, simultaneous strong and/or repeated nerve signals along neighboring nerve cells stimulate growth of new junctions (synapse) between those nerves.  These serve to associate new experiences with old, establishing what is recalled when long term memory is triggered.  (Brain Chemistry and Memories)

  6. When a similar nerve signal is later received in the brain, these association connections function as pattern comparisons, and recognition.  Some we describe as pain while some we recognize by memory as plèasurable.

  7. It is postulated that those signals that we find to be plèasurable are because they are associated with memory signals from bodily needs met either recently or more likely when the nervous system first developed.

Dopamine

It was earlier thought that a key aspect of plèasure is the developed synaptic junctions between certain neurons in the brain which release of the neurotransmitter dopamine and other neurotransmitters.  As discussed in Memories, repeated or extended experiences cause the growth of long term memory synapse connections between adjacent neurons.  Sensations which are plèasurable are often related to the release of dopamineBerridge and Robinson This molecule transmits the signal between previously connected neurons but also promotes growth of additional synapses resulting in learned perception of plèasure.  While several aspects of plèasure normally occur intermingled in several parts of normal brain function, in 1998 Kent C. Berridge and Terry E. Robinson (at right→) proposed that dopamine was actually involved in what they called incentive salience which is the motivation of wanting the experience as distinct from the actual liking of the experience.  While dopamine may be responsible for learning plèasure in anticipation of an experience, dopamine does not itself provide the direct perception of the plèasure of liking the experience although usually the two occur together.  Other similar neurotransmitter chemicals such as serotonin, GABA and endorphins also contribute to the process.

Rather than the former paradigm that dopamine was telling us to feel good, dopamine role is to recognize what is salient, i.e., the anticipation of expected bits of new information we need to pay attention to in order to survive, like alerts about sex, food and other plèasures, as well as danger and pain.  If you are hungry and you get a whiff of frying meat, dopamine is released.  But dopamine is also released if a lion leaps towards you.  Dopamine's role is to shout: "Hey! Pay attention to this!"  The whisper "Wow, this feels great" might be only the afterthought.
tyrosine to dopamine

Dopamine (←see structures at left) is synthesized mainly by nervous tissue and adrenal glands by addition of Oxygen (from water) to the amino acid tyrosine converting it to L-DOPA.  The subsequent removal of CO2 from L-DOPA results in dopamineDopamine functions as a neurotransmitter carrying nerve signals between neurons and at higher concentrations indirectly promoting the growth of new synapses.  It also serves as a hormone transmitting signals between organs via the blood, and as a precursor for making other hormones: epinephrine (adrenaline) and norepinephrine (noradrenaline).

The brain is routinely flooded with information arriving from the body's nerve sensors.  Most of that is repetitious routine information which is promptly ignored.  But when a neuron in the nucleus accumbens portion of the brain detects the arrival of either an unusually rare signal or one of particular significance based on past experiences, dopamine is released by neuron synapses resulting in heightened awareness and short term and potentially long term learning.  Such learning associated with enjoyment can make the accompanying behavior more likely to reoccur.  Stimuli such as food and sèx cause neurons to release dopamine.  Drugs such as cocaine and amphetamines also directly or indirectly increase dopamine concentration in synapse.  Thus by triggering anticipatory desire and motivation (wanting) dopamine is involved in craving more of the drug.  Dopamine is also released anticipating avoiding or removing an unpleasant stimuli, suggesting that is somehow also equivalent to plèasure.  On the other hand, limiting dopamine concentrations reduces motivation and consequentially results in reduced ability to experience plèasure.  The salience theory of dopamine also helps explain other self-destructive tendencies such as binge eating and gambling.  It also helps explain why we crave the stimulation of new information.

There are several types of receptors on the neurons which receive a signal carried by dopamine across a synapse.  D1 and D5 receptors increase cyclic adenosine monophosphate (cAMP) concentrations and typically enhance further nerve signal.  D2, D3 and D4 reduce cyclic AMP and typically reduce further nerve signal.  All such dopamine receptors are G proteins which are coupled to other proteins in the neuron's membrane.

Plèasure hypothesis

Dopamine's Role

Dopamine is known to precede the sensation of plèasure, rather focusing the subconscious to remember whatever preceded that sensation.  It both acts as a neurotransmitter, carrying the nerve signal across the synapse (creating short term memory), and at higher concentration due to repeat or prolonged experience, as a hormone promoting the growth of new synapse (creating long term memory). 

Plèasure chain linkages

The actual sensation of plèasure is not dopamine or any other chemical.  Plèasure is more likely a web of linked memories (via synapses) of what our nervous system defines by learning to be plèasurable experiences.  Our first plèasure may have originated when a new nerve began monitoring the satisfaction of our prenatal need for nurishment.  Other early plèasures such as warmth, touch, and pressure in the womb were associated through the growth of synaptic connections between brain neurons which were simultaneously stimulated.  Thus we were born with a handful of previously established plèasures  The taste of the first milk after birth provided new association with those earlier plèasures, increasing the number of synapse connections.  Repeated associations strengthen the memory, the stongest of which get perpetuated by pion like proteins.  Whenever we have an additional experience that we associate with previous plèasures, we add that new synaptic connect to the chain of plèasure linkages.  So what we call plèasure is not be a static sensation, but a burst of nerves signals through the vast connected links of plèasure memories.  Such plèasure grows as we gain new but related plèasurable experiences.

Like other memories which fade over time (forgotten) if not recalled and reinforced, some weaker links to our earlier plèasurable experiences may also fade with time.  And the most routine sensations such as breathing to provide for our need of Oxygen and removal of Carbon dioxide may fade from being enjoyable much as our brain ignors other monotinous sensory input.  This frees our conscious awareness for activities less certain to occur such as finding and eating food.  This process leaves the rarest of experiences to be most pleasurable.

Sèxûal Plèasure

Sèxûal activities are for many people among the most plèasurable.  Why is that?  All of these heighten the experience.

Plèasure and Pain

Pain appears to be a hardwired component of our nervous systems with the primary purpose of alerting us to injury or potential injury.  We have sensory neurons with dedicated HRPV1 proteins embedded in their outer membranes which both detect acids and some other potentially harmful substances, alert to high temperatures, and mediate the transmission of other pain signals.  But if the plèasure hypothesis is correct, signals of pain can also be associated with previously established plèasures and themselves become plèasurable.  Large numbers of people have learned to enjoy mildly uncomfortable or painful experiences.  For example many people add pepper or other hot spices to foods, stimulating HRPV1 proteins to report the stinging, mildly painful, hot taste.  Some people learn to enjoy even very painful experiences.  If that is true, it may be possible for people with chronic pain such as arthritis to learn to associate a previously established plèasure with the pain to provide some plèasure to make their pain more tolerable.

It is also possible to associate the removal or relief of pain with previously established plèasures. 

Reminder about Certainty in science

It may be appropriate here to recall the nature of certainty in science.  Scientists are keenly aware that the processes they use do not establish absolute truth.  Explanations are developed to account for observations.  Predictions are derived from those explanations and further observations or careful measurements done to verify if the predictions are correct, thus implying some validity of the explanations.  By repeatedly predicting and checking, alternative explanations are ruled out and confidence is gained for the explanation.  Sometimes predictions are not verified requiring explanations to be amended or replaced.  The end result is not absolute understanding, but theories which have withstood much testing and warrant much confidence.  Human beings (and presumably many other animals as well) live their lives by making countless decisions bases on our theoretical understandings of our world.  Theories are critical for productive, successful lives, even if they are not absolute truth.

Scientists usually provide some indication of how certain they are about a given statement.  But understanding the amount of certainty often requires careful reading (or listening) and attention to language clues.  Some theories such as the structural formula of dopamine have so much certainty that scientists refer to them as facts.  Other ideas such as the possible mechanism of plèasure currently have much less evidence so remain largely hypotheses.

Investigation

KuhnScience progresses in several distinct stages as describes by a number of science historians such as Thomas Kuhn (b1922, d1996, at right→).  Kuhn suggested that currently accepted theories imply various possible observations and measurements which might confirm the validity of the theories and often enhance their value and applicability.  However sometimes such observations and measurements reveal that reality is a bit different than the theories predicted.  In such cases the usual procedure is to make small modifications to the theories so their implications and predictions are again in accord with reality.  This routine of science often continues for centuries or more.

But occasionally discordant observations and measurements amass without adequate theoretical revisions until some scientists perceive that the theory is wrong and needs replacement.  Even so, the old understanding is never abandoned until someone proposes a theory that seems to have the potential for better matching reality.  Such times of scientific revolution are both traumatic and exciting.  Rarely is there ever universal agreement that the proposed theory is the answer.  Many who learned and have worked their entire lives successfully with the older theory continue to see its value rather than potential value in the new theory.  Sometimes only upon the deaths of the old-school scientists does a new theory finally reach a consensus of validity.

We could now be approaching a time of revolution in the human understanding of plèasure.  It appears the previous understanding was inconsistent with evidence about the workings of the nervous system.  Perhaps the new paradigm will be much superior.

Procedure

The creative process has never been clearly outlined.  Once a theory is proposed, there are clear procedures for predicting probable observations and the results of key measurements.  Those observations and measurements can then be made and checked against the predictions to determine if the new theory is successful.  But creating a successful theory is largely a matter of preparation followed by awaiting inspiration, insight, and (in religious terms) revelation.  But in the past, successful theories almost always come from people who are aware of the previous theory and its failings, and very knowledgeable about all the aspects of reality that the theory should explain.

  1. You might want to consider the processes of several famous scientists:
    Dmitri Mendeleev used known facts about the chemical elements to create the periodic chart.
    Nicholas Copernicus knew Ptolemy's understanding of heavenly motion but rejected one of his basic assumptions as unreasonable.
    Albert Einstein expected Maxwell's laws to be consistent whether the observer was moving past an electric charge or not.
  2. You might also wish to practice by forming a theory about each of the following series, then predicting the next 3 in each series:
    1, 2, 3, 4, 5, ... (trivial!  The theory is that these are successive numbers.  So the next are 6, 7, and 8...)
    1, 4, 9, 16, 25, ...
    A, E, F, H, I, K, L, M,...
    18, 46, 94, 63, 52, ...
    O, T, T, F, F, S, S, ...
    D, N, O, S, A, J, J, ...
  3. When you discover or hear a theory that clearly is successful, there is an ah ha that is often pleasantly experienced.  It might be noted that there may be (as definitely is the case of the second series) more than one successful theory!

  4. With that preparation, perhaps you are ready to tackle developing a better, or more elaborate theory of plèasure?

Communicating technical information such as observations and findings is a skill used by scientists but useful for most others.  If you need course credit, use your observations in your journal to construct a formal report.

References

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created 18 June 2006
latest revision 27 January 2010
by D Trapp

The check of a theory is whether it makes successful predictions.  The next in each series is 6, 36, N (but not n), 61, E, and M.  And as frustrating as it is, God never tells us if our theories are REALLY right!
Mac made