Schizophrenia nigrostriatal dopamine pathway

The first generation antipsychotics, now known as typical drugs, were all D2 receptor blockers and, as such, very likely to produce Parkinsonian side effects. Because antipsychotic potency was associated with D2 receptor affinity, it was assumed that dopamine overactivity was the essential defect in schizophrenia and that a direct dopamine blockade was the definitive route to treatment. But these drugs affected both the target dopamine pathways of the mesolimbic projection and the uninvolved nigrostriatal projection. Unfortunately, that meant that movement disorders were the price that had to be paid for antipsychosis. 

Here is one last word about L-dopa. It delivers dopamine to the entire brain, not just the nigrostriatal pathway. We know from our previous discussion that excess dopamine activity is associated with schizophrenia. It should not surprise you then that a rather common side effect of L-dopa is some of the symptoms of schizophrenia, including hallucinations. 

Fig. 19.3 Sagittal brain section illustrating dopaminergic pathways. I. Mesolimbic pathway (overactive in psychotic illness according to the dopamine hypothesis of schizophrenia).VTA= ventrotegmental area. 2. Nigrostriatal pathway (involved in motor control, underactive in Parkinson s Disease and associated with extrapyramidal motor symptoms). 3. Tuberoinfundibular pathway (inhibits prolactin release from the hypothalamus).

The nigrostriatal pathway and the limbic system also seem to be involved in behavioural effects, and there is evidence that schizophrenia in humans is associated with dopaminergic hyperactivity, and dopamine receptor antagonists are used as antipsychotic agents see dopamine... 

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