The brain dopamine (DA) system is central to numerous behavioral processes, including movement, learning, and motivation. Dopamine is involved in mediating the reactivity of the organism to the environment at different time scales, from fast impulse responses related to reward via slower changes with uncertainty, punishment, and possibly movement to the tonic enabling of postsynaptic motor, cognitive, and motivational systems deficient in Parkinson's disease.
DOPAMINERGIC RECEPTORS
- G protein-coupled dopamine receptors (D1, D2, D3, D4, and D5) mediate all of the physiological functions of the catecholaminergic neurotransmitter dopamine, ranging from voluntary movement and reward to hormonal regulation and hypertension.
- Pharmacological agents targeting dopaminergic neurotransmission have been clinically used in the management of several neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, bipolar disorder, Huntington's disease, attention deficit hyperactivity disorder (ADHD(1)), and Tourette's syndrome.
DOPAMINE AND MOTIVATION
- Dopamine is often considered as a pleasure chemical of the brain.
- Dopaminergic neurons respond to rewarding stimuli which include primary rewards like opioids or food, or more abstract forms of reward like cash rewards or pictures of pretty faces.
DOPAMINE AND INFLAMMATION
- Inflammatory cytokines affect the basal ganglia and dopamine to mediate depressive symptoms related to motivation and motor activity.
- A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation.
DOPAMINE AND ADICTION
- With Habitual intake of addictive drugs, dopamine receptors expressed in the brain are decreased, thereby reducing interest in activities not already stamped in by habitual rewards.
- Dopamine contributes to addiction and obesity through its differentiated roles in reinforcement, motivation and self-regulation, referred to here as the 'dopamine motive system', which, if compromised, can result in increased, habitual and inflexible responding.
DOPAMINE, PARKINSON, AND SCHIZOPHRENIA
- The molecular mechanisms causing the loss of dopaminergic neurons containing neuromelanin in the substantia nigra and responsible for motor symptoms of Parkinson's disease are still unknown. Dopamine oxidation to dopamine o-quinone, aminochrome and 5,6-indolequinone plays an important role in neurodegeneration in Parkinson's disease since they induce mitochondria and protein degradation dysfunction; formation of neurotoxic alpha synuclein protofibrils and oxidative stress.
- A decrease in DA in the substantia nigra of the brain has been implicated as the cause of Parkinson.
- A functional excess of DA or oversensitivity of certain DA receptors is one of the causal factors in schizophrenia.
OTHER FUNCTIONS OF DOPAMINE
- In the eye, DA modulates ciliary blood flow and aqueous production, which impacts on intraocular pressure and glaucoma.
- In the cardiovascular system, DA increases blood pressure and heart activity, mostly through a stimulation of adrenoceptors, and induces vasodilatation in the renal circulation, possibly through D1R stimulation.
- In pancreatic islets, beta cells store DA and co-release it with insulin. D1R is mainly expressed in beta cells, where it stimulates insulin release, while D2R is expressed in both beta and delta cells (in the latter at higher level), where it inhibits, respectively, insulin and somatostatin release.
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