Chronic haloperidol and chlorpromazine treatment alters in vitro β-endorphin metabolism in rat brain

To determine if chronic haloperidol (3.0 mg/kg per day) or chlorpromazine (4.2 mg/kg per day) treatment alters central β-endorphin metabolism, haloperidol and chlorpromazine were perfused via Alzet^TM minipumps into male Sprague-Dawley rats for 8 days. Crude twice-washed membranes, purified synaptic plasma membranes and Golgi-enriched membranes, respectively, were isolated from rat brains and time course incubated with β-endorphin. All samples were analyzed by high resolution, reversed-phase high performance liquid chromatography. The half-lives of β-endorphin for animals treated with haloperidol or chlorpromazine were not statistically different from control animals at the crude washed membranes. At the purified synaptic plasma membranes, however, the half-lives of β-endorphin from haloperidol (t _{1 2} = 45.1 min)- and chlorpromazine (t _{1 2} = 47.0 min)-treated animals were significantly decreased as compared to the control animals (t _{1 2} = 78.0 min). The half-life of β-endorphin at the Golgi-enriched membranes was increased for haloperidol (t _{1 2} = 112.3 min) and chlorpromazine (t _{1 2} = 103.0 min)-treated animals when compared to control animals (t _{1 2} = 80.2 min). The findings indicate a differential effect of the dopamine receptor antagonists haloperidol and chlorpromazine on the extracellular fate at the synaptic plasma membranes of β-endorphin and the intracellular processing at the Golgi-enriched membranes in vitro.