Good ole dopamine! Watch out, major geek alert ahead and it involves some biochemistry. I think everyone just clicked off, but hold that mouse as this will be a short crash course some cool stuff.
Dopamine is neurotransmitter with five flavors of dopamine receptors — D1, D2, D3, D4 and D5, and their variants. It works on the sympathetic nervous system (think "fight, flight or freeze"), producing effects such as increased heart rate and blood pressure. It canNOT cross the blood-brain barrier, so dopamine given as a DRUG (via injection etc) does not directly affect the central nervous system. To get around this, patients that need it (such as in Parkinson's disease) may take L-DOPA which is a precursor to dopamine.
Dopamine is also a precursor of norepinephrine (noradrenaline) and epinephrine (adrenaline) which qualifies it as a card carrying member of the catecolamine family. .
How does the body make it?
It is made in the body via hydroxylation (think oxidizing) the amino acid L-tyrosine to L-DOPA and then on to dopamine, which can then in turn go on to norepinephrine (noradrenaline) and epinephrine (adrenaline).
Can I increase dopamine without drugs?
Some have used L-tyrosine to possible increase dopamine levels, although more research is needed in this area. There are very few studies done on it and most seem to be split in terms of L-tyrosine enhancing exercise performance. One researcher I spoke to at ACSM this past year was quite convinced that L-tyrosine would enhance exercise performance based on his review of the literature (source: personal conversation).
Functions in the brain
Dopamine does tons of stuff in the brain. Everything from motor activity, motivation/reward, sleep, mood, learning and on down the list--yep, it is important!
Dopamine is commonly associated with the pleasure system of the brain, providing feelings of enjoyment. Drugs like cocaine and amphetamines inhibit the RE- UPTAKE of dopamine; so there is more floating around in the brain to do its job. Cocaine is a dopamine transporter blocker that competitively inhibits dopamine uptake to increase the lifetime of dopamine and augments an overabundance of dopamine (an increase of up to 150 percent) within the parameters of the dopamine neurotransmitters; aka it cranks up the dopamine in your brain by a crap load!
Amphetamines are similar in structure to dopamine and sort "mimic it" They can actually enter presynaptic neuron and then shove the poor dopamine molecules out of their storage vesicles! Think of them as a drill sargent shoving you out of bed in the AM to get to work.
Obviously both of these drugs have consequences (like what goes up must come down) and are illegal. Although I remember asking my neuroscience prof a few years back that if Parkinson's patients have an issue with dopamine, what happens if you give them cocaine? I was actually serious!
We know that the body and mind are highly integrated. Below are some new abstracts showing the connection between exercise (movement) and dopamine. Be sure to check out a previous blog I did recently on Mood and Mobility.
Thoughts?
Neuroplasticity of dopamine circuits after exercise: implications for central fatigue.
Foley TE, Fleshner M. Department Integrative Physiology, Center for Neuroscience, Clare Small Building, University of Colorado-Boulder, Boulder, CO 80309-0354, USA.
Habitual exercise increases plasticity in a variety of neurotransmitter systems. The current review focuses on the effects of habitual physical activity on monoamine dopamine (DA) neurotransmission and the potential implication of these changes to exercise-induced fatigue. Although it is clear that peripheral adaptations in muscle and energy substrate utilization contribute to this effect, more recently it has been suggested that central nervous system pathways "upstream" of the motor cortex, which initiate activation of skeletal muscles, are also important. The contribution of the brain to exercise-induced fatigue has been termed "central fatigue." Given the well-defined role of DA in the initiation of movement, it is likely that adaptations in DA systems influence exercise capacity. A reduction in DA neurotransmission in the substantia nigra pars compacta (SNpc), for example, could impair activation of the basal ganglia and reduce stimulation of the motor cortex leading to central fatigue. Here we present evidence that habitual wheel running produces changes in DA systems. Using in situ hybridization techniques, we report that 6 weeks of wheel running was sufficient to increase tyrosine hydroxylase mRNA expression and reduce D2 autoreceptor mRNA in the SNpc. Additionally, 6 weeks of wheel running increased D2 postsynaptic receptor mRNA in the caudate putamen, a major projection site of the SNpc.
These results are consistent with prior data suggesting that habitually physically active animals may have an enhanced ability to increase DA synthesis and reduce D2 autoreceptor-mediated inhibition of DA neurons in the SNpc compared to sedentary animals. Furthermore, habitually physically active animals, compared to sedentary controls, may be better able to increase D2 receptor-mediated inhibition of the indirect pathway of the basal ganglia.
Conclusion: Results from these studies are discussed in light of our understanding of the role of DA (monoamine dopamine) in the neurobiological mechanisms of central fatigue.
Elevated central monoamine receptor mRNA in rats bred for high endurance capacity: implications for central fatigue.
Foley TE, Greenwood BN, Day HE, Koch LG, Britton SL, Fleshner M. Department of Integrative Physiology, University of Colorado, Boulder, CO 80309 0354, USA. teresa.foley@colorado.edu
Although alteration to peripheral systems at the skeletal muscle level can contribute to one's ability to sustain endurance capacity, neural circuits regulating fatigue may also play a critical role. Previous studies demonstrated that increasing brain serotonin (5-HT) release is sufficient to hasten the onset of exercise-induced fatigue, while manipulations that increase brain dopamine (DA) release can delay the onset of fatigue. These results suggest that individual differences in endurance capacity could be due to factors capable of influencing the activity of 5-HT and DA systems.
We evaluated possible differences in central fatigue pathways between two contrasting rat groups selectively bred for high (HCR) or low (LCR) capacity running. Using quantitative in situ hybridization, we measured messenger RNA (mRNA) levels of tryptophan hydroxylase (TPH), 5-HT transporter (5-HTT), 5-HT1A and 5-HT1B autoreceptors, dopamine receptor-D2 (DR-D2) autoreceptors and postsynaptic receptors, and dopamine receptor-D1 (DR-D1) postsynaptic receptors, in discrete brain regions of HCR and LCR. HCR expressed higher levels of 5-HT1B autoreceptor mRNA in the raphe nuclei relative to LCR, but similar levels of TPH, 5-HTT, and 5-HT1A mRNA in these areas. Surprisingly, HCR expressed higher levels of DR-D2 autoreceptor mRNA in the midbrain, while simultaneously expressing greater DR-D2 postsynaptic mRNA in the striatum compared to LCR. There were no differences in DR-D1 mRNA levels in the striatum or cortex between groups.
Conclusion: These data suggest that central serotonergic and dopaminergic systems may be involved in the mechanisms by which HCR (high capacity running) have delayed onset of exercise-induced fatigue compared to LCR (low capacity running).
Running wheel exercise enhances recovery from nigrostriatal dopamine injury without inducing neuroprotection.
O'Dell SJ, Gross NB, Fricks AN, Casiano BD, Nguyen TB, Marshall JF. Department of Neurobiology and Behavior, 1452 McGaugh Hall, University of California, Irvine, Irvine, CA 92697, USA. sjodell@uci.edu
Forced use of the forelimb contralateral to a unilateral injection of the dopaminergic neurotoxin 6-hydroxydopamine can promote recovery of motor function in that limb and can significantly decrease damage to dopamine terminals. The present study was conducted to determine (1) whether a form of voluntary exercise, wheel running, would improve motor performance in rats with such lesions, and (2) whether any beneficial effects of wheel running are attributable to ameliorating the dopaminergic damage. In experiment 1, rats were allowed to run in exercise wheels or kept in home cages for 2 1/2 weeks, then given stereotaxic infusions of 6-hydroxydopamine into the left striatum. The rats were replaced into their original environments (wheels or home cages) for four additional weeks, and asymmetries in forelimb use were quantified at 3, 10, 17, and 24 days postoperatively. After killing, dopaminergic damage was assessed by both quantifying 3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester ([(125)I]RTI-55) binding to striatal dopamine transporters and counting tyrosine hydroxylase-positive cells in the substantia nigra.
Exercised 6-hydroxydopamine-infused rats showed improved motor outcomes relative to sedentary lesioned controls, effects that were most apparent at postoperative days 17 and 24. Despite this behavioral improvement, 6-hydroxydopamine-induced loss of striatal dopamine transporters and tyrosine hydroxylase-positive nigral cells in exercised and sedentary groups did not differ. Since prior studies suggested that forced limb use improves motor performance by sparing nigrostriatal dopaminergic neurons from 6-hydroxydopamine damage, experiment 2 used a combined regimen of forced plus voluntary wheel running. Again, we found that the motor performance of exercised rats improved more rapidly than that of sedentary controls, but that there were no differences between these groups in the damage produced by 6-hydroxydopamine.
Conclusion: It appears that voluntary exercise can facilitate recovery from partial nigrostriatal injury, but it does so without evident sparing of dopamine nerve terminals.
