The blockade of 5-HT1A receptors in the ventral tegmental area inhibited morphine/dextromethorphan-induced analgesia in pain rat models

The aim of the present study was to determine the involvement of the VTA 5-HT1A receptors in analgesia induced by the co-administration of morphine and dextromethorphan (DM). Male Wistar rats were bilaterally cannulated in the VTA by the stereotaxic instrument. The tail-flick and formalin tests were performed to assess nociception in the acute and tonic pain conditions respectively. The present data indicated that intraperitoneal (i.p.) administration of morphine increased the tail-flick latency (1-4 mg/kg) and decreased the pain score of formalin test (2-8 mg/kg), showing an analgesic effect. Co-administration of ineffective doses of morphine (1 or 2 mg/kg) with DM (30 mg/kg, i.p.) induced analgesia in both animal models. Interestingly, intra-VTA microinjection of 5HT(1A) receptors antagonist, S-WAY100-135 (0.5 and 1 mu g/kg), inhibited the analgesic effect of morphine plus DM in both acute and tonic pain models. It should be considered that the same doses of DM or S-WAY100-135 by itself had no effects on antinociception in the animal models. Overall, these results indicated that systemic blockade of NMDA receptors via DM administration potentiated the response of a low dose of morphine to induce analgesic effect. Additionally, it seems that the VTA serotonergic system via 5HT(1A) receptors mediates the potentiative effect of DM on morphine-induced analgesia.