The DopamineHypothesis III acknowledges that the driving force of schizophrenia is due tomultiple pathways that lead to excessive presynaptic hyper dopaminergic functioning,howeverit fails to recognise what regulates dopamine behaviour. Dopamine synthesis hasbeen linked to faulty glutamate NMDAR receptors giving a clearer indicationinto how dopamine levels are fluctuated. The fact that antipsychotic drugs onlyblock D2 receptors with at least 30% of individuals failing to respond tomedication indicates that other mechanisms currently not targeted are a resultof the initial problems not being treated.
In order to study the effects ofglutamate on schizophrenia, HMRS and PET imaging have been used. Dopamine regulation is sensitive towardsglutamate, indicating that changes in glutamate levels by blocking NMDARreceptors mediates dopamine activity. By doing so it puts a wider understandingof how dopamine is regulated in the pre frontal cortex and hippocampus.
Studiesusing ketamine have been of particular interest as the drug blocks the NMDARreceptor causing dysregulation of glutamate leading to an increased sensitivityof dopamine. Poels et al (2013) found that in healthy controls when givenketamine there was an NMDAR blockade on striatal dopamine release leading tosimilar cognitive impairments, negative and positive symptoms likewise to thoseseen in schizophrenia (Coyle, 2006). As a result, supports that dopamineregulation should be targeted further downstream at the NMDAR to reduceschizophrenic symptoms by increasing activity at their sites, to benefit thosewho are unable to respond to antipsychotics. While research is plausible, thereare limitations when using H-MRS. Although a popular technique used inschizophrenia they are not able to distinguish between intra or extracellularcompartments, limiting how specific the results are. Radiotracers are far ablerto give insight into specific areas, indicating that future research shouldfocus on these techniques in order to strengthen the data to further understandthis complex system.
Individuals may be more sensitive to glutamate deficiency,implying that these mechanisms must be targeted to control dopamine functioningif individual does not respond to antipsychotics. Although thedopamine hypothesis III seems plausible, negative symptoms and cognitivedeficits need to be accounted for more widely. As the hypothesis has been re-workedthroughout the years, this is most likely going to happen in the future as techniquesare enhanced leading to more accurate results. However, by accepting the role of dopamine asthe biggest contributor to the onset of schizophrenia, it is easy to rationalizethe use of drugs such as antipsychotics to treat positive symptoms (Read, Mosherand Bentall, 2005).
It is hard to imagine schizophrenia diagnosed and treatedwithout dopamine at the forefront, due to its response to antipsychotics in dampeningits effects giving great accountability to the neurochemical imbalance in thebrain. Nevertheless, as there are a several individuals’ who aretreatment-resistant, this leaves many individuals still suffering with positivesymptoms, and the majority still unable to reach full benefits due to theirpersistent negative and cognitive symptoms (Lally et al., 2016). However, bytaking into account different aspects of the dopamine hypothesis III and dopaminesensitivity due to NMDAR receptors, it enables us to target different stages ofthe illness by using a selection of treatments.
Overall, dopamine can bedescribed as the driving force of schizophrenia, and acknowledging itsinteractions with risk factors to schizophrenic symptoms will only strengthen research.