The possible role of dopamine in phenothiazine-induced hypothermia in rats: an application to DA hypothesis of schizophrenia.

Hypothermic effects of d-Amphetamine, chlorpromazine, a variety of other phenothiazines, ET495 and haloperidol in rats at 4 degrees C were measured separately and in combination. All the drugs produced some hypothermia. Among the phenothiazines, degree of hypothermia induced was found to be correlated with relative effectiveness of the drug as an antipsychotic agent. Hypothermic effects of each of the phenothiazines in combination with d-Amphetadrugs as an antipsychotic agent. Hypothermic effects of each of the phenothiazines in combination with d-Amphetamine was greater than for either drug alone. Hypothermic effects of the combination CPZ with Amphetamine was potentiated by haloperidol but blocked by ET495. The evidence supports a model of neuronal feedback loops either within the central DA mesolimbic pathway or between the mesolimbic and nigrostriatal DA systems. The establishment of interdependency between antipsychotic and hypothermic effects of phenothiazines offers promise not only to a greater understanding of the mechanisms underlying these effects, but the possibility of an objective test for screening new materials for antipsychotic effectiveness.