Morphine and other opioids are among the most effective prescription medications for the treatment of pain. Addiction and hyperalgesia associated with their long-term use limits the clinical utility of these drugs. In view of a role of somatodendritic serotonin-1A receptors in addiction and analgesic effects of morphine, the present study concerns effects of co-use of buspirone, a partial agonist at the serotonin-1A receptor, on reinforcing, hyperalgesic, and motor effects of morphine in rats. A dose of morphine (7.5 mg/kg) producing moderate effects on motor activity and analgesia, and buspirone (doses of 0, 1.0, and 2.0 mg/kg) were injected intraperitoneally. Reinforcing effects were monitored in a conditioned place preference (CPP) paradigm and associated changes in motor activity were monitored during a drug conditioning phase. The hot plate test was used to monitor nociceptive response. Acute administration of morphine decreased motor activity and reduced pain perception. Repeated administration was reinforcing in the CPP paradigm and was associated with hyperalgesia and tolerance in motor depressant effects of morphine. These effects of repeated morphine administration were blocked in rats cotreated with buspirone. Pain perception was also slightly reduced in rats repeatedly treated with higher doses of buspirone. The findings are important for improving and extending therapeutic medications for pain.

The present study shows an important role of serotonin-1A receptors in morphine-induced hyperalgesia and addiction. It shows that buspirone, a prescription medicine for anxiety and depression can block addictive and hyperalgesic effects of morphine. Clinicians should consider buspirone as adjunctive therapy with morphine to improve therapeutic medications in pain.