Enhancement of morphine-induced analgesia after repeated injections of methylenedioxymethamphetamine.

Repeated administration of methylenedioxymethamphetamine (MDMA) to rats results in long-term depletion of serotonin (5-hydroxytryptamine; 5-HT) in several brain regions. Because of the apparent role of 5-HT in morphine-induced antinociception, the present experiment was designed to determine the effects of repeated MDMA injections on morphine-induced analgesia. Rats (n = 48) received 8 s.c. injections (one every 12 h for 4 days) of MDMA (20 mg/kg) or saline (1.0 ml/kg). Two weeks after the last injection, the groups were divided into 4 subgroups that received either saline, or morphine 2.5, 3.55 or 5.0 mg/kg (s.c.). Nociception was assayed before and after saline or morphine administration by the method of tail immersion in warm water (55 degrees C). The day after analgesia testing, the animals were sacrificed, brains and spinal cords removed and 5-HT, norepinephrine (NE) and dopamine (DA) levels in various brain and spinal cord regions were assayed. The analgesic effect of morphine was enhanced in rats that had received repeated MDMA injections. MDMA selectively depleted 5-HT in the cortex, hippocampus, striatum, brainstem and in the cervical portion of spinal cord. However, 5-HT levels were not changed in the thoracic and lumbar segments of the spinal cord. Thus, a functional consequence of repeated MDMA administration in rats was to enhance morphine-induced antinociception in association with reductions in brain and cervical spinal cord 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)