OPIOID REGULATION OF PROOPIOMELANOCORTIN (POMC) GENE-EXPRESSION IN THE RAT-BRAIN AS STUDIED BY IN-SITU HYBRIDIZATION

Proopiomelanocortin (POMC) is the precursor of the potent opioid pepti de beta-endorphin as well as a number of other active peptides. On the basis of neuroanatomical data indicating the presence of contacts bet ween POMC neurons in the rat arcuate nucleus,3,7 it has been proposed that POMC neurons could be autoregulated. In order to investigate the role of opiates in the regulation of POMC gene expression in the rat a rcuate nucleus, we studied the effects of chronic administration of th e opioid drug morphine and an opiate receptor antagonist naloxone on P OMC mRNA levels as measured by in situ hybridization. 4-day treatment with naloxone (4 mg/kg/day) produced a 60% increase in the number of s ilver grains overlying POMC neurons. Conversely, morphine (40 mg/kg/da y) also administered during 4 days decreased the hybridization signal by 30%. The concomitant administration of morphine and naloxone comple tely prevented the effect of morphine on POMC gene expression indicati ng that the inhibitory influence of morphine is likely to be mediated by opioid receptors. The data obtained clearly indicate that activatio n of opioid receptors decreased the biosynthetic activity of POMC neur ons and that conversely opiate receptor blockade caused an increase in the activity of these neurons. They are consistent with the hypothesi s of an autoregulation of the POMC neuronal system by endogenous opiat e peptide(s).