Brain endorphin levels increase after long-term chlorpromazine treatment

Abstract

Observations in animals (Bloom et al., 1976; Jacquet and Marks, 1976) and man (Terenius et al., 1976; Gunne et al., 1977; Kline et al., in press) suggest the possible involvement of brain endorphins in mental illness. Terenius et al. (1976) reported that four chronic schizophrenics exhibited elevated levels of endorphins in their cerebrospinal fluid during ‘a symptom-rich’ phase of their disease. In two of these patients, whose condition improved during neuroleptic therapy, there was a return to low endorphin level (Gunne et al., 1977). These findings are consistent with the idea that some psychotic symptoms might be caused by excessive endorphin activity. We report here raised endorphin levels in brains of rats after long-term administration of the antipsychotic agent chlorpromazine (CPZ), but not after the structurally-related antidepressant imipramine. This raises the possibility that the therapeutic action of antipsychotics may be associated with changes in endorphin activity.