Ribonuclease protection assays were performed on the basal hypothalamus (BH), the preoptic area (POA) and the thalamus (THAL) from female guinea pigs that were ovariectomized and implanted with morphine (n = 8) or placebo (n = 8) pellets for 1 week. An antisense [32P]rUTP labeled riboprobe, representing a 280 bp fragment of the guinea pig mu-opioid receptor gene (spanning putative TM II through eight residues of TM IV), protected a single RNA band of 280 bp. In contrast to the rat, the guinea pig THAL expressed less mu-opioid receptor mRNA than both POA and BH. Morphine treatment caused a significant decrease (15.6 +/- 5.8%) in mu-opioid receptor mRNA expression in the BH, while POA and THAL were not different from placebo controls. Therefore, in conjunction with our previous findings of a downregulation of mu-opioid receptors, mu-opioid receptor mRNA is downregulated in the mediobasal hypothalamus of female guinea pigs following chronic morphine treatment.