Dopamine resistance
Dopamine or 2-(3,4-dihydroxyphenyl)ethaneamine (IUPAC name) is a catecholamine that acts as a neurotransmitter (and sometimes as a hormone) at various sites in the bodies of humans and animals. The name is an abbreviation of the IUPAC name, with the f becoming a p in English.
Dopamine can be formed from the amino acid tyrosine. The first step in this process is the conversion of tyrosine into levodopa by the enzyme tyrosine hydroxylase. It is then decarboxylated by the enzyme DOPA decarboxylase to form dopamine.[1] It also occurs in the human and animal organism as a precursor of the hormones adrenaline and norepinephrine, which can be formed from them by hydroxylation.
It plays an important role in reward-motivated behavior in executive functions, motivation, arousal, reinforcement and reward. Dopamine also effects in the brain motor control as well as lower functions including breastfeeding, sexual arousal and nausea. Dopamine in popular culture and media is the neurotransmitter for experiencing happiness, pleasure, joy and well-being. [2]
There are nerve pathways in the brain that are sensitive to this transmitter such as the frontal lobe and basal ganglia. The breakdown is by means of the enzymes monoamine oxidase and aldehydroxydase and in the process homovanillic acid is produced. Also, dopamine can be converted to norepinephrine in the adrenal medulla by the enzyme dopamine hydroxylase and then norepinephrine can be methylated back to adrenaline.[3]
Content
- Anatomy of dopaminergic circuits
- Dopamine, effect and cognitive performance
- Dopamine and behavioral disorders
- Dopamine and addiction
Anatomy of dopaminergic circuits
Several dopaminergic circuits have been found in the brain:
- The nigrostriatal circuit. This circuit is mainly involved in the regulation of motor activity. It runs from midbrain in the substantia nigra specifically from the pars compacta to the dorsal part of the striatum to the frontal brain regions.
- The mesolimbic circuit. This circuit has a function primarily in the regulation of emotional behavior, particularly behavior determined by reward system. It originates in nuclei of the tegmentum and projects through the ventral part of the striatum (called nucleus accumbens) to structures in the frontal brain that are part of the limbic system (such as the cortex cingularis anterior).
- The mesocortical circuit. This circuit too has its origin in the area tegmentalis ventralis, and projects to the cortex orbitofrontalis and the cortex cingularis anterior in the frontal brain.
- The cortex orbitofrontalis is also part of the limbic system, and plays a role in motivation and emotional responses.
- The posterior part of the hypothalamus has dopamine neurons extending to the spinal cord
- The nucleus arcuatus and the nucleus periventricularis in the hypothalamus to the pituitary gland, inhibiting the secretion of prolactin
- The zona incerta in the hypothalamus stimulates the release of gonadotropin-releasing hormone necessary to the development of the male and female reproductive systems [2]
The physiological effects of dopamine depend on binding to one of five different subtypes of dopamine receptors, of which the D1 and D2 receptors are the best known,[4] which have different locations in the brain. For example, D1 receptors are found in the striatum and neocortex, and D2 receptors are found mainly in the striatum and limbic system.
Drugs like cocaine and medications like methylphenidate inhibit the presynaptic reuptake of dopamine, leaving more dopamine in the synapse cleft and causing overstimulation of dopamine pathways (especially the mesolimbic circuit). These drugs also stimulate so-called opiate receptors. Their cells have the property of overriding the inhibitory effect of certain neurotransmitters (such as GABA).
The Dopamine transporter reabsorbs the free dopamine in synaptic cleft into the supplying nerve fiber, lowers the concentration and thus regulates that the impulse stops.
Dopamine, effect and cognitive performance
Positive affect, such as a pleasant feeling after reward, has been shown to have a beneficial effect on cognitive performance. According to Ashby's theory[5], a circuit in the brain plays a role in this where dopamine is released in the basal ganglia and then transported to the frontal brain regions and drives reward-motivated learning and behavior.
Dopamine is most commonly released when filling desire and motivates consuming, hedonistic, behavior. Dopamine release also depends on rewards that are unexpected or greater than expected. High levels of dopamine lead to high levels of motor activity and impulsive behavior.
Dopamine then also acts as a "learning" signal. After an action with an increase in dopamine activity, the basal ganglia circuit is altered so that the same response can be more easily evoked when similar situations occur in the future. This is a form of operant conditioning.
The basal ganglia and dopamine play a central role in the theory of "action" selection w hen a person or animal is in a situation where multiple behaviors are possible. activity in the basal ganglia determines which of them will be performed, by releasing that response from inhibition as they continue to inhibit. Basal ganglia and dopamine in this model are responsible for initiating behavior, they essentially form a decision-making system. [2]
Dopamine and behavioral disorders
People with Parkinson's disease are deficient in dopamine. This mainly involves the nigrostriate circuit. Because dopamine cannot be absorbed directly by the brain, the dopamine precursor levodopa is used as a drug. From the levodopa in the blood, the body itself can then make more dopamine in the brain.
The book Awakenings (Oliver Sacks, 1973) and its film adaptation (Penny Marshall, 1990) describe the effect of levodopa as a drug in a rare syndrome Encephalitis lethargica.
Even with normal aging, there is reduced functioning of dopamine, both in the basal ganglia and in projections to the limbic system and prefrontal cortex.[6] This is thought to have implications for the decline of complex motor and cognitive functions in old age.
Dopamine imbalance is also likely in ADHD. Medications include the agonist dextro-amphetamine and reuptake inhibitor methylphenidate.
Dopamine also plays a role in schizophrenia and psychosis. In the brains of schizophrenics, after autopsy, low concentrations of D2 receptors have been found in the striatum, among others.[7] According to Weinberger, over- and under-activations of the mesolimbic and mesocortical circuits, respectively, play a role in two of the most characteristic aspects of schizophrenia, namely the so-called positive -and negative symptoms.[8] The antipsychotic amisulpride a dopamine receptor antagonist is used to treat this. Dopamine is not the only neurotransmitter that plays a role in schizophrenia. Acetylcholine and serotonin also play a role, as evidenced by the mechanism of action of the atypical antipsychotic clozapine.[9] The importance of the neurotransmitters GABA and glutamate is evidenced by research into the development of new drugs to treat schizophrenia.[10]
In the brains of extroverts, stimuli such as reward appear to involve a relatively strong response of dopamine.[11]
Dopamine and addiction
Dopamine measurements in addicts show a disturbed dopamine balance. When an addict uses his drug, he makes more dopamine than a non-addict.
One drug developed for this purpose, for example, is Bupropion, a selective inhibitor of neuronal reuptake of dopamine and norepinephrine used to support smoking cessation.
Treatment BeterKlinic
BeterKliniek is the clinic for Integrative Medicine that bridges regular and non-regular medicine.
An van Veen (physician) and Michael van Gils (therapist) look for the cause of a condition or disease. That is where the treatment starts otherwise, as people often say, it is 'carrying water to the sea'. We call this cause medicine. Sometimes it is also desirable to treat the symptoms (at the same time). We call this symptom medicine.
Chronic disorders often have their cause in epi- genetics. You can schedule a free informative telephone consultation (phone number 040-7117337 until 1 p.m.) at BeterKliniek to discuss your symptoms so that we can provide you with further advice.
