The hallmark symptoms of
schizophrenia include profound disturbances in thought, perception, cognition etc., which negatively impacts an individual's quality of life. Current
antipsychotic drugs are not effective in treating all symptoms of this disorder, and often cause severe movement and metabolic side effects. Consequently, there remains a strong impetus to develop safer and more efficacious
therapeutics for patients, as well as elucidating the etiology of
schizophrenia. Previous work in our lab has introduced a novel candidate for the treatment of this disease: the
dopamine D2 receptor (D2R) allosteric modulator, 3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (
PAOPA). We have previously shown that
PAOPA, by selectively modulating D2R, can ameliorate
schizophrenia-like symptoms in animal models, although the precise mechanism is presently not understood.
Synapsin II is a presynaptic vesicular
protein which has been strongly implicated in
schizophrenia, as it is reduced in the prefrontal cortex of patients, and knockdown of this
protein elicits
schizophrenia-like phenotypes in animal models. Given the
therapeutic effects of
PAOPA and the role of
synapsin II in
schizophrenia, the objective of this study was to investigate the effect of chronic administration of
PAOPA (45 days) on neuronal
synapsin II protein expression in rodents. Immunoblot results revealed that the
synapsin IIa, but not the IIb
isoform, was increased in the dopaminergic regions of the striatum, nucleus accumbens, and medial prefrontal cortex. The results of this study implicate a role for modulation of
synapsin II as a possible therapeutic mechanism of action for potential
antipsychotic drug PAOPA.