Effect of morphine on proenkephalin gene expression in the rat brain

Previous studies indicate that an acute injection of morphine does not effect the level of opioid peptides and their mRNA in the brain. However, due to the presence of a large pool of mRNA and possible opposing changes in turnover rate it is often difficult to visualize the transitory and relatively small alterations in gene transcription by examining mRNA level. Therefore, in situ hybridization with probes directed against intronic sequences to measure the primary transcript of proenkephalin (PPE) mRNA (heteronucleic RNA, hnRNA) in the rat brain following morphine administration was used in this study. The distribution of the hybridization signal of probes against both the A and B intron of the PPE gene were identical and coincide with the distribution PPE mRNA. Thus, to increase the sensitivity of this assay both probes were concurrently hybridized. Female and male Sprague- Dawley rats were gonadectomized and injected with morphine (10 mg/kg, SC). We detected no changes in PPE mRNA levels in the striatum, olfactory tubercle (OT) and n. accumbens core (NAC) at any time following morphine administration. However, from 0.5 h until 24 h following morphine injection, the levels of PPE hnRNA in NAC and OT but not in the dorsal striatum were significantly decreased. The level of c-fos mRNA was increased only in the dorsal striatum following morphine injections. These data show that morphine administration can acutely change opioid peptide gene transcription. The observed decrease of PPE hnRNA levels for 24 h following a single morphine injection may indicate its importance for the development of acute and chronic dependence. However, the significance of these alterations in PPE gene transcription in term of the acute effect of morphine is not clear, because the steady-state level of mRNA was not changed.