Bioinformatics Research Laboratory, IBI Biosolutions Pvt. Ltd. India
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The Dopamine pathways
Dopamine is the neurotransmitter used by the reward pathway (also called the mesolimbic pathway, which is closely associated with the mesocortical pathway). But there are two other important pathways in the brain that utilize dopamine: the nigrostriatal pathway and the tuberoinfundibular pathway. Generally, drugs that affect dopamine levels in the brain affect all three of these dopamine pathways.
Cortico-striatal projections are not dopaminergic pathways per se, but instead represent the modulating influence that the prefrontal cortex -especially the premotor and motor areas and the orbito-frontal areas - have on the normal dopamine-related functioning of the basal ganglia.
Cortico-striatal projections from the premotor/motor cortex to the putamen are involved in basic volitional motor planning and motor action. They regulate the more automatic and involuntary aspects of movement that originate in the putamen and related structures.
Cortico-striatal projections from the orbitofrontal cortex to the caudate are involved in the inhibitory control of one's thoughts and actions. They regulate the more automatic and primitive impulsive/compulsive aspects of behavior that originate in the caudate and related structures.
The Mesocortical pathway is a neural pathway that connects the ventral tegmental area (VTA) of the midbrain to the prefrontal cortex, especially the dorsolateral prefrontal cortex. It is one of the four major dopamine pathways in the brain. It is essential to the normal cognitive function of the dorsolateral prefrontal cortex (part of the frontal lobe), and is thought to be involved in motivation and emotional response, attention, initiative, planning, decision making, working memory, and other higher cognitive functions. Meso-cortical dopamine projections help to regulate and modulate these functions. The meso-limbic and meso-cortical pathways meet, intersect, and intertwine with each other, and can be thought of as being "in balance" within the brain. A lesion in the meso-cortical tract in animals, which prevents dopamine from getting to the prefrontal cortex, results in an increase in dopamine activity in the meso-limbic tract. This indicates that the prefrontal cortex (PFC) normally acts as a brake on activity in limbic system structures.
This pathway is thought to be associated with the negative symptoms of schizophrenia, which include avolition, alogia and flat affect (lack of emotional response).This pathway is closely associated with the mesolimbic pathway, also known as the reward pathway.
Mesolimbic pathwayThe Mesolimbic pathway is one of the neural pathways in the brain that links the DA-producing cells in the ventral tegmentum (VTA) in the midbrain to the nucleus accumbens (NA), which is located in the striatum and is a part of the limbic system and the amygdala. It is one of the four major pathways where the neurotransmitter dopamine is found.
The mesolimbic pathway is thought to be involved in social emotional behavior and motivation, producing pleasurable feeling, and is often associated with feelings of reward and desire, particularly because of the connection to the nucleus accumbens, which is also associated with these states. Because of this, this pathway is heavily implicated in neurobiological theories of addiction. However, recent research has pointed towards this pathway being involved in incentive salience rather than euphoric mood states.
The mesolimbic pathway is one of the major pathways targeted by antipsychotic medication. Although the process is not fully understood, it has been found that disruption of dopamine function (particularly, an excess of dopamine) in this area has been linked to psychosis and the 'positive symptoms' of schizophrenia (particularly delusions and hallucinations). Successful antipsychotic medication is therefore thought to have its effect by blocking dopamine receptors in this pathway.
Dopamine neurons are lost in the mesolimbic pathway in Parkinson's Disease; however, they are lost far more quickly in the nigrostriatal pathway, and, because deficits do not become apparent until a reduction of 80-90% in the numbers of neurons, their loss here is asymptomatic.
Nigrostriatal pathwayThe Nigrostriatal pathway is a neural pathway that projects from cell bodies within the substantia nigra to the caudate and putamen (corpus striatum). These structures are components of the basal ganglia and are part of the extrapyramidal motor system within the brain. It is one of the four major dopamine pathways in the brain, and is particularly involved in the production of movement, as part of a system called the basal ganglia motor loop.The basal ganglia are involved in the regulation and coordination of automatic aspects of body movements, such as initiating movement, putting your feet out in front of each other to walk forward in a smooth and synchronized manner, reaching for objects, and other sequencing actions. Loss of dopamine neurons in the substantia nigra is one of the main pathological features of Parkinson's disease, leading to a marked reduction in dopamine function in this pathway. The symptoms of the disease typically do not show themselves until 80-90% of dopamine function has been lost.
This pathway is also implicated in producing tardive dyskinesia, one of the side-effects of antipsychotic drugs. These medications (particularly the older typical antipsychotics) block D2 dopamine receptors in multiple pathways in the brain.The desired clinical effect of reducing psychotic symptoms is thought to be associated with blocking dopamine function in the mesolimbic pathway only. However, as many of these drugs are not selective, they block dopamine in all pathways. When this happens in the nigrostriatal pathway, similar movement problems to those found in Parkinson's disease can occur.
Tuberoinfundibular pathwayThe Tuberoinfundibular (hypothalamic-pituitary) pathway refers to a population of dopamine neurons in the arcuate nucleus of the mediobasal hypothalamus (the 'tuberal region') that project to the median eminence (the 'infundibular region'). It is one of the four major dopamine pathways in the brain. Dopamine released at this site regulates the secretion of prolactin from the anterior pituitary gland i.e its release in the hypothalamic-pituitary pathway leads to the inhibition of release of the hormone prolactin from the pituitary. Prolactin is an important reproductive hormone that stimulates breast tissue and promotes lactation.
Some antipsychotic drugs block dopamine in the tuberoinfundibular pathway, which can cause an increase in blood prolactin levels (hyperprolactinemia). This can cause abnormal lactation (even in men), disruptions to the menstrual cycle in women, visual problems, headache and sexual dysfunction.
