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Enhancement of morphine-induced analgesia after repeated injections of methylenedioxymethamphetamine
P Nencini1, W L Woolverton, L S Seiden
1Department of Psychiatry, University of Chicago, IL 60637.
Abstract:
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)
Insights
Repeated MDMA administration in rats enhanced morphine analgesia by depleting serotonin (5-HT) in the brain and spinal cord. This study investigates the long-term effects of MDMA on pain perception and neurotransmitter levels.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Methylenedioxymethamphetamine (MDMA) causes long-term serotonin (5-HT) depletion in rat brains.
- Serotonin plays a role in morphine-induced antinociception (pain relief).
Purpose of the Study:
- To investigate the effect of repeated MDMA administration on morphine-induced analgesia.
- To examine the long-term changes in serotonin, norepinephrine, and dopamine levels following MDMA exposure.
Main Methods:
- Rats received repeated subcutaneous injections of MDMA (20 mg/kg) or saline over 4 days.
- Two weeks later, rats were tested for analgesia using the tail immersion method after receiving saline or varying doses of morphine.
- Neurotransmitter levels (5-HT, NE, DA) were measured in brain and spinal cord regions.
Main Results:
- Repeated MDMA administration significantly enhanced morphine-induced analgesia.
- MDMA selectively depleted 5-HT in the cortex, hippocampus, striatum, brainstem, and cervical spinal cord.
- No significant changes in 5-HT levels were observed in the thoracic and lumbar spinal cord segments.
Conclusions:
- Repeated MDMA exposure enhances morphine antinociception in rats.
- This enhancement is associated with long-term reductions in brain and cervical spinal cord serotonin levels.