Morphine induces short-lived changes in G-protein gene expression in rat prefrontal cortex.

We have utilized a reverse transcriptase-polymerase chain reaction (RT-PCR) methodology followed by enzymatic restriction analysis to detect changes in G-protein mRNA levels in morphine-treated rats. The relative distribution of mRNA levels for Galpha(o) Galpha(i1), Galpha(i2), Gbeta(1) and Gbeta(2) in the nucleus accumbens, striatum, locus coeruleus and prefrontal cortex was found to be similar to that previously estimated with other techniques. Morphine-induced changes of G-protein mRNA levels were detected only in the prefrontal cortex. Acute treatments (30 mg/kg, intraperitoneally) resulted in a significant increase of Galpha(o) mRNA and significant decreases of Galpha(i1) and Galpha(i2) mRNAs. Chronic morphine administration (10-50 mg/kg over 14 days, intraperitoneally) increased Gbeta(1) and Galpha(i1) and Galpha(i2) mRNAs levels to 148%, 410% and 451% of control, respectively. G-protein mRNA returned to control levels within 48 h of termination of the chronic treatments. The morphine-induced changes in G-protein mRNA levels may reflect changes in gene expression and could result in changes in G-protein levels affecting signal transduction pathways in chronically treated animals.