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Summary The 4bT-endorphin fragments, des-tyrosine-γ-endorphin (DTγE) and α-endorphin, exert behavioral activities which in some aspects are comparable to those induced by haloperidol and amphetamine respectively. However, the peptides do not mimic the effects of the drugs in particular on gross behavior. It is suggested that the balance between DTγE and α-endorphin plays a significant role in controlling behavioral responses of the organism.

Acquisition of heroin self administration is facilitated by reduced body weight and by a fixed time food delivery schedule. The introduction of these environmental factors did not markedly influence either the ED50 for heroin self-administration or the amount of drug intake over graded dose levels. Previous studies suggest the latter variables can serve as an index of opiate reinforcing efficacy. Thus, it might be that weight reduction and scheduled food affect the rate of acquisition of heroin intake more than they affect the reinforcing efficacy of the drug.

Publisher Summary This chapter describes the antipsychotic action of γ-type endorphins and the characterization of the patients responding to treatment with these peptides, and the animal research aimed at the mode and site of their antipsychotic action. The three strategies for developing new antipsychotic drugs are discussed in view of the available data on γ-type endorphins. The currently isolated and identified endorphins, endogenous substances with morphine-like actions, belong to three major families, arising from three distinct systems: the pro-enkephalin, the pro-opiomelanocortin, and the pro-dynorphin system. The research on γ-type endorphins, both in the clinical and the animal studies, has contributed to the development of more refined animal models of schizophrenia and of animal tests for searching the possible antipsychotic substances. The collected data on γ-type endorphins strongly point to neuroendocrine characteristics in schizophrenia. The neuropeptides implicated in this disease may not be limited to γ-type endorphins, because it is shown that peptides related to cholecystokinin are active in animal tests predicting antipsychotic action and relieve psychotic symptoms in a number of schizophrenic patients.

SUMMARY The neuroleptic-like peptide (des-enkephalin)-γ-endorphin (DEγE, βLPH 66–77 ) has potential antipsychotic activity and interferes with certain DA receptor systems in the nucleus accumbens, which are sensitive to low doses of apomorphine. This may serve to link the γ-type endorphin and the dopamine hypothesis of schizophrenia.