1Cademy - Effect of Antipsychotics on Schizophrenic Behavioral Phenotypes in DRD2 Mouse Mutants

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Effect of Antipsychotics on Schizophrenic Behavioral Phenotypes in DRD2 Mouse Mutants

DRD2 agonist quinpirole didn’t change the level of excitatory afferant stimulation, but it did significantly decrease inhibitory afferant activity in DRD2 mutant mice. This generated an excitatory/inhibitory imbalance in response to afferant activation - causing an increase in this ratio, which may lead to an increase in the response of pyramidal neurons when afferant activity arrives.
Total locomotion was reduced down to basal levels in both controls and DRD2 mutants when risperidone was used in combination with amphetamine or NMDAR antagonist MK-801, which suggests that risperidone antagonism on DRD2 may have prevented the effect of massively released dopamine and that DRD2 expression in parvalbumin interneurons wasn’t required by risperidone to lower locomotor activity
When treated with aripiprazole in combination with amphetamine, controls saw a significant decrease in total locomotion but only a partial decrease in DRD2 conditional mutants
When treated with aripiprazole in combination with MK-801, control mice saw a significant decrease in locomotion but DRD2 mutants were resistant to aripiprazole treatment - which indicates that DRD2 expression on parvalbumin interneurons is required by this particular antipsychotic to recover from induced hyperlocomotion.

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Updated 2022-08-24

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