Diazepam effects on striatal met-enkephalin levels following long-term pharmacological manipulations

As measured by highly specific radioimmunoassay, long-term treatment of rats for 28 days with benzodiazepines resulted in a significant increase in the striatal met-enkephalin content, which was opposite to the decrease in this area observed after acute administration. Other areas investigated i.e. the hypothalamus, the medulla oblongata/pons and the midbrain, were unchanged after chronic benzodiazepine treatment. Acute diazapam challenge of these animals revealed a considerable degree of tolerance towards the acute drug effect. In rats chronically treated with morphine for 28 days, acute diazepam administration no longer decreased striatal met-enkephalin, in contrast to rats receiving ethanol for the same time, in which the diazepam-induced decrease was potentiated.