Biphasic dose-related effects of morphine on dopamine release

The effects of morphine on extracellular dopamine levels in brain have never been studied over a wide range of doses within a single study. This has made it difficult to make definitive interpretations of drug interactions with morphine. An inhibition of morphine-induced increases in dopamine could be interpreted as either antagonism or potentiation depending the shape of the morphine dose-response curve. Accordingly, the aim of the present study was to determine the effects of a wide range of morphine doses (0, 5, 10, 20 and 30 mg/kg, i.p.) on extracellular dopamine, DOPAC and HVA levels in the nucleus accumbens and striatum of awake and freely moving female Sprague-Dawley rats. The results show that, in both brain regions, the dose-response curve for morphine-induced increases in dopamine is non-monotonic while the dose-response curve for morphine-induced increases in DOPAC and HVA is monotonic in the nucleus accumbens. The results of this study are discussed in terms of their implications for interpreting drug interactions with morphine and with relationship to morphine's mode of action at mu and kappa opioid receptors.