In schizophrenia there is hippocampal dysregulation of dopamine system function. Part of the deficit that arises from the changes in hippocampal structure in development is the loss of GABAergic inhibition in the hippocampus (Meyer, 2019). This results in a strong excitatory drive of glutamate from the hippocampus to the Nucleus Accumbens (NAcc) (Meyer, 2019). Therefore, there is far too much disinhibition of the ventral pallidum by the NAcc, which results in increased activation of dopamine neurons in the ventral tegmental area (VTA) to the NAcc (Meyer, 2019). This is known as the hypoglutamate hypothesis of Schizophrenia (Meyer, 2019). The VTA is comprised of two major kinds of cells: spontaneously active cells; and cells under tonic inhibition by the ventral pallidum (population neurons) (Meyer, 2019).
The activity state of the ventral subiculum is dependent on environmental context (Meyer, 2019). When activated, it disinhibits the ventral pallidum, therefore removing the ventral pallidum’s inhibitory influence on the dopamine neurons of the VTA (Meyer, 2019). This increases the firing rates of DA neurons in the VTA (Meyer, 2019). Thus, it sets the gain of the dopamine system that influences our perception and actions for behaviorally relevant stimuli (Meyer, 2019). When a behaviorally relevant stimuli arrives, it results in the excitatory inputs from the pedunculopontine tegmental nucleus (PPT) to send cholinergic and glutaminergic drive to the hippocampus (Meyer, 2019). In fact, the population neurons can become spontaneously active allowing burst firing in the dopamine neurons to go and influence the system (Meyer, 2019). In summary, controlling the number of dopamine neurons firing spontaneously controls the gain of the system that is able to respond when any behaviorally relevant signal arrives.
Drugs that Treat Psychosis
Henri Laborit, a French surgeon during World War II, noticed that antihistamines had a sedative effect (Linda, 2017). He later collaborated with a pharmaceutical company creating a specialized phenothiazine in order to reduce psychosis in patient’s post-surgery (Linda, 2017). The medication he used was called chlorpromazine (CPZ), and he later observed that it caused a state of sedation in the patients, but without narcosis (Linda, 2017). Impressed by this observation, Laborit used this medication to reduce psychosis in patients who experienced severe psychotic symptoms (Linda, 2017). This resulted in a major advancement in the use of this drug to treat various symptoms of psychosis.
