A job could be auspicious when it matches motives
I would like to start writing this by describing my recent experience in job-hunting.
After a pile of unsuccessful job applications, I was called for an interview at last, for a position of technical translator. I am a novice to translation jobs; so no work has yet been promised but I was given an opportunity to prove that I qualify to meet the demand by sufficiently translating a few test materials given. The subjects were unfamiliar and unrelated to my interests, and so I have been attempting to read around, to get some relevant background information.
Minor intellectual challenges associated with it allowed me going on for a short while, but I soon found it tiring to maintain focus on topics that do not interests me. Somehow disproportionally exhausted, I was left with a sinking feeling when the attempts of translating made me feel as if I am turning into some kind of an automaton. More than anything I missed the subjects familiar to me; then I had to revisit my usual playground of biological sciences to make myself feel human again.
Reading, on the subjects that fascinates one, is a completely different experience. The joyful process seems endless as always there will be new questions of which answers need to be searched for. In the iterative processes of search, retrieval, and organising, I could easily lose myself and forget the rest. As all the excitements somehow seem to cancel out any fatigue, the activity could easily be carried out as long as that takes if circumstances allow me to do so.
Clearly, there is a fine coordinated biochemistry happening then, to mesmerise one into the activity. I propose the culprits here to be three monoamines: serotonin, dopamine and noradrenaline. In a minimal explanation, serotonin and dopamine bring the feeling of being rewarded and content, and noradrenaline helps maintaining focus and alertness at right doses.
Three monoamines: serotonin, dopamine and noradrenaline
5-hydroxytryptamine (5-HT: serotonin), dopamine (DA), and noradrenaline (NA), are neurotransmitters biosynthesised from amino acids tryptophan, phenylalanine or tyrosine. Appropriate hydroxylation and decarboxylation of tryptophan yields 5-HT, whilst that of tyrosine makes DA, which becomes NE via another hydroxylation.
The synthesis is regulated by the end-product inhibition, meaning the specific enzymatic activity (of hydroxylase etc.) is reduced by high cytosolic concentration of the product in the axon terminal whilst these are stored. When monoamines are released promptly, the elevated intracellular calcium concentration (as a result of transmitter release) up-regulates the enzyme to restock the transmitters.
5-HT (serotonin)
5-HT is generally associated with positive effects on mood conditions. Several agents are currently available to treat acute depression by increasing the synaptic availability of 5-HT; but the therapeutic efficacy of these compounds, selective-serotonin re-uptake inhibitors (SSRIs), may not actually be that great (Kirsch et al., 2008). The rapid increase in SSRI sales did not significantly decrease the suicide rates in four Nordic countries in an overall trend between the early 90s and 2006, though whether the committed were on the medication remains unknown (Zahl et al., 2010); someone with no hope but a death wish may unlikely visit a doctor. In addition to the positive affective effects, 5-HT has a property of emesis induction by acting on its ionotropic receptor.
DA (dopamine)
DA is well-known for its role in what perceived as rewarding or motivating, as dopaminergic neurones in the ventral tegmental area of the midbrain release DA to the basal forebrain area (i.e. the mesocorticolimbic dopamine system). The downside of the system manifests when the reinforcing tendency turns into an addiction. That could happen in responses to stimuli which raises DA at the synapses. For instances, opioids and nicotine stimulate DA release as the dopaminergic neurones have opioid receptors and nicotinic acetylcholine receptors, and cocaine prolong DA availability by preventing its re-uptake at the terminal notably in the nucleus accumbens.
(NA) Noradrenaline
NA has several roles in both central and peripheral systems.
At synapses, it limits excitatory transmission by glutamate (Scheiderer et al. 2003; 2008). The peripheral action of NA could increase alertness, startle response and decrease sleep.
The restoring fine balance in the co-existing three might be more helpful than simply interfering with one of them
Currently, affective disorders such as depressions are often dealt with SSRI prescription. But, as mentioned above, the effectiveness of the treatment has been questioned. That might suggest that an artificial up-regulation of a single neurotransmitter may not be appropriate or sufficient to restore motivations, aspirations, and willingness: the missing components in the affective condition like major depression. There have been recent developments in the triple re-uptake inhibitor of the three monoamines (Caldarone et al., 2010, Nathan et al., 2010; Prins et al., 20011; Shao et al., 2011). In future such compounds might possibly provide an effective treatment for those in desperate needs when administered carefully; however, individual tendencies and plausible genetic susceptibility towards relevant conditions (e.g. addictions, substance misuse etc.) must be taken into account.
What makes one attaches to certain specific subjects and why?
I vaguely ponder of the questions and relate that to our innate curiosity and craving for understanding unknowns. It could merely be that we all enjoy doing what we are capable of reasonably well-comprehending. The nature of specificity, how various subjects are selected by a range of individuals, appears largely diverse. Undoubtedly, these variations in the brain structure and chemistry allowed humans to develop extensively to live in the societies with multi-functional features. We should better appreciate all individual differences existing therein.
An attempt to discuss these three neurotransmitters from a different perspective would be made in another opportunity sometime.
References
Caldarone BJ. et al., 2010. The novel triple reuptake inhibitor JZAD-IV-22 exhibits an antidepressant pharmacological profile without locomotor stimulant or sensitization properties. J Pharmacol Exp Ther 335(3):762-70. (NOT open access)
Kirsch I. et al., 2008. Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. PLoS Medicine 5(2) e.45.
Nathan PJ. et al., 2010. Neuropsychiatric Adverse Effects of Centrally Acting Antiobesity Drugs. CNS Neurosci Ther (NOT accessible: abstract viewable at Entrez pubmed).
Prins J. et al., 2011.The potential and limitations of DOV 216,303 as a triple reuptake inhibitor for the treatment of major depression: a microdialysis study in olfactory bulbectomized rats. Pharmacol Biochem Behav 97(3):444-52.
Scheiderer CL, Dobrunz LE, and McMahan LL, 2003. Novel Form of Long-Term Synaptic Depression in Rat Hippocampus Induced By Activation of alpha1 Adrenergic Receptors. J Neurophysiol 91:1071–1077.
Scheiderer CL et al., 2008. Coactivation of M(1) muscarinic and alpha1 adrenergic receptors stimulates extracellular signal-regulated protein kinase and induces long-term depression at CA3-CA1 synapses in rat hippocampus. J Neurosci 28:5350–5358.
Shao L. et al., 2011. Discovery of N-methyl-1-(1-phenylcyclohexyl)ethanamine, a novel triple serotonin, norepinephrine and dopamine reuptake inhibitor. Bioorg Med Chem Lett.
Zahl PH et al., 2010. The relationship between sales of SSRI, TCA and suicide rates in the Nordic countries. BMC Psychiatry, 10:62.
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