PSYC1004 Lecture Notes - Lecture 6: Dopamine Hypothesis Of Schizophrenia, Glutamine, Nucleus Accumbens
26 Oct 2018
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Glutamine and dopamine interaction in schizophrenia
Both dopamine and glutamate interact on the level of cortical function, particularly in
regulatory circuits which encompass the prefrontal cortex, midbrain, and striatum, all of
which are which are relevant for the pathogenesis of schizophrenia, and manifestation of its
symptoms (Tost & Meyer-Lindenberg, 2011). This interaction suggests that instead of
looking at each hypothesis as a separate entity, perhaps pin pointing the cause of
schizophrenia depends on looking at how dopamine and glutamate interact to cause
symptoms associated with schizophrenia, as it is natural that both glutamate and dopamine
interact within the brain (Tost & Meyer-Lindenberg, 2011). Through the use of
neuroimaging, certain dopaminergic and glutamatergic risk genes (a genetic variant that
increases the risk of developing certain diseases) have been identified. Dopamine-
Glutamate abnormalities have been linked to the variation of both catechol-O-
methyltransferase (COMT) and D-amino-acid oxidase activator (DAOA) (Brisch et al., 2009).
These variants are believed to modulate synaptic dopamine, and alter glutamate signalling
(Brisch et al., 2009). The additive combination of these two risk variants are believed to
affect both memory and learning by gating the information flow in the dorsal striatum and
nucleus accumbens (Tost & Meyer-Lindenberg, 2011). On top of the knowledge that certain
risk genes cause abnormalities in both dopamine and glutamine, causing symptoms
commonly associate with schizophrenia, it is also believed that abnormalities in the
glutamate pathways may influence the activity of dopamine (West, Floresco, Charara,
Rosenkranz & Grace, 2003). In particular, the glutameric activation of striatonigral feedback
pathways which go on to affect the activity of dopamine cells in the mid brain. This
interaction is crucial in directing information between the limbic and motor regions of the
brain (Laruelle, 2014). It is believed that the above glutamate-dopamine interaction
interferes with the feedback pathway, thus effecting how information is relayed, resulting in
psychomotor slowing, a symptom associated with schizophrenia. (West, Floresco, Charara,
Rosenkranz & Grace, 2003). This same interaction, means that an abnormality in glutamate,
goes on to directly impact the levels of dopamine in the striatal complex, a cluster of
neurons which are associated with movement, and the feeling of rewards/pleasure, both of
which are affected in schizophrenia (Tost & Meyer-Lindenberg, 2011). Furthermore,
abnormal glutamate levels are believed to cause abnormal dopamine neurotransmission,
which effect a range of physical and physiological functions such as heart rate, mood, sleep
