Dopamine receptors in the anterior cingulate cortex implicate in nicotine enhanced morphine analgesia

It is well known that the anterior cingulate cortex (ACC) plays an important role in acute pain perception. In the present study, we aimed to investigate the possible involvement of the ACC dopamine D1 and D2 receptors in nicotine plus morphine-induced analgesia. The ACC’s of adult male Wistar rats were bilaterally cannulated by stereotaxic instrument and the tail-flick test was used to measure the thermal pain threshold. The results indicated that subcutaneous (s.c.) injection of nicotine (0.3 mg/kg) potentiated the analgesic response of intraperitoneal (i.p.) administration of morphine (3 mg/kg). Systemic administration of the same doses of nicotine or morphine alone had no effect on tail-flick latency. Intra-ACC administration of apomorphine (0.3–0.9 μg/rat), the non-selective D1/D2 receptors agonist, plus ineffective doses of nicotine (0.1 mg/kg, s.c.) plus morphine (3 mg/kg, i.p) induced analgesia in rats. In addition, the analgesia induced with co-administration of nicotine and morphine was inhibited via intra-ACC administration of SCH23390 (0.5–1 μg/rat) or sulpiride (0.5–2 μg/rat), the selective antagonists of D1 or D2 receptors, respectively. The intra-ACC microinjection of the same doses of drugs alone had no effect on tail-flick latency. Cubic interpolation analysis also confirmed that activation or inactivation of the ACC D1 and D2 receptors by different doses of drugs can modulate the nicotine-morphine analgesic response. The findings suggest that the ACC has an important role in acute thermal pain perception and modulates the analgesia induced by nicotine plus morphine via dopaminergic receptors.