Limbic system mesolimbic pathway

The nucleus accumbens is part of the limbic system. It receives dopaminergic input through the mesolimbic system that originates from cell bodies in the ventral segmental area (A 10 cell group). This mesolimbic dopaminergic pathway is part of the reward pathways. Drugs of abuse (cocaine, amphetamine, opiates or nicotine) have been shown to increase the level of dopamine release in these neurons. 

The mechanism by which 5-HT2 antagonism could ameliorate schizophrenic symptoms and what effect 5-HT has on mesolimbic and mesocortical pathways through A10 neurons is even less certain. It is more likely that 5-HT s action occurs postsynaptically in the limbic system or PFC. The probability that neuroleptics benefit from a particular balance of DA and 5-HT2A antagonism is developed later. 

Dopaminergic neuromodulatory system. The neurons that synthesize dopamine (structural formula in box) are found in the midbrain, from which they project to the limbic system (the mesolimbic pathway), the cerebral cortex (the mesocortical pathway), as well as to the extrapyramidal motor system (the nigrostriatal pathway). 

The net effect is to push the brain in a very REM dream-like direction. PET studies of schizophrenic patients brains show deficient frontal cortical activation and limbic overactivation. The working hypothesis of schizophrenia investigators is that psychosis results when the overactive mesolimbic pathway is released from deficient cortical control. This is formally identical to our hypothesis of dream psychosis the dorsolateral prefrontal cortex is deactivated and the limbic system is hyperactivated. 

Schizophrenia appears to be caused by an overactivity of dopamine pathways in certain parts of the brain such as the limbic system.2,23 This idea is based primarily on the fact that most antipsychotics block dopamine receptors, thereby reducing dopaminergic hyperactivity in mesolimbic pathways and other limbic structures (see the next section of this chapter). The increased dopamine influence underlying psychosis could be caused by excessive dopamine synthesis and release by the presynaptic neuron, decreased dopamine breakdown at the synapse, increased postsy-naptic dopamine receptor sensitivity, or a combination of these and other factors. 

The distribution of dopamine in the brain is very non-uniform. There is some in the limbic system, and a large proportion is found in the corpus striatum - a part of the extrapyramidal motor system which is concerned with the coordination of movement. Dopamine-containing nerves are found in three main pathways in the brain. The nigrostriatal pathway contains about 75% Of the dopamine in the brain, and the cell bodies lie in the substantia nigra and the nerves terminate in the corpus striatum. The second important pathway is the mesolimbic pathway, the cell bodies of which lie in the mid-brain and project to parts of the limbic system, particularly the nucleus accumbens. The third, the tubero-infundibular system, consists of short neurons that run from the arcuate nucleus of the hypothalamus to the median eminence and the pituitary gland, the secretions of which they regulate. 

The mesolimbic and mesocortical pathways are dopamine-containing neurones that run from an area in the midbrain called the ventral tegmentum to the limbic system and the prefrontal area of the cerebral cortex respectively. These are areas of the brain that are normally involved in behavioural and emotional functions. 

Through the pathways of the mesolimbic system (a term introduced by Ungerstedt in 1971), the basal ganglia provide an interface with limbic brain regions. This interface has been repeatedly implicated in psychiatric diseases, such as schizophrenia and other affective disorders, as well as in reward and addiction. 

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