Changes in Opioid and Cannabinoid Receptor Protein following Short-Term Combination Treatment with D9-Tetrahydrocannabinol and Morphine

Recent studies in our laboratory have shown that in mice, low doses of morphine in combination with D9-tetrahydrocannabi-nol (D9-THC) have a similar antinociceptive effect to high doses of morphine alone. After short-term administration of this com-bination, there is no behavioral tolerance to the opioid. Previous binding studies and Western analyses following chronic mor-phine exposure in rodent models indicate significant m-receptor down-regulation, as well as decreased levels of receptor pro-tein, in both brain and spinal cord regions. We hypothesized that combination-treated animals would show no receptor pro-tein down-regulation. The levels of opioid (m, d, k) and canna-binoid (CB1) receptor protein were evaluated in mouse models of short-term exposure to D9-THC, morphine, or both drugs in combination. Western blot analysis revealed that all three type