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 G alpha (o) G alpha (i1) G alpha (i2) G beta (1) and G beta (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 G alpha (o) mRNA and significant decreases of G alpha (i1) and G alpha (i2) mRNAs. Chronic morphine administration (10-50 mg/kg over 14 days, intraperitoneally) increased G beta (1) and G alpha (i1) and G alpha (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. (C) 2001 Elsevier Science B.V. All rights reserved.