Antipsychotic-like effects independent of D2 receptor blockade: the case of alstonine

VM. LINCK; AP. HERRMANN; MC. ANTONELLI; CO. OKUNJI; E. ELISABETSKY.

Florencia

Conferencia; 3rd Schizophrenia International Research Society Conference; 2012

International Research Society

D2 dopamine blockage is the one common feature in the mechanism of action of all known antipsychotics. Although coherent for the mesolimbic dopamine hyperactivity associated with schizophrenia, the D2 blockade leads to unwanted side effects; more importantly, it does not counteract the frontal cortex hypofunctioning dopamine circuits believed to be responsible for negative and cognitive symptoms in schizophrenics. Ideally, an antipsychotic would decrease dopamine transmission at limbic areas, but increase it at cortical structures, which could be achieved by indirectly modulating dopamine pathways. Antipsychotics-­‐like effects were characterized for the alkaloid alstonine in relevant animal models (including positive, negative and cognitive symptoms). Based on the antipsychotic-­like behavioral profile of alstonine in mice, we suggested that alstonine modulates dopamine independently of D2 antagonism. The aim of this study was to further investigate this proposition, by looking into prolactin plasma levels, as well as D2 receptors and dopamine transporter density in specific brain areas of mice treated with alstonine.