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Morphine-induced changes in histamine dynamics in mouse brain
Abstract:
The effect of the acute morphine treatment on histamine (HA) pools in the brain and the spinal cord was examined in mice. Morphine (1-50 mg/kg, s.c.) administered alone caused no significant change in the steady-state levels of HA and its major metabolite, tele-methylhistamine (t-MH), in the brain. However, depending on the doses tested, morphine significantly enhanced the pargyline (65 mg/kg, i.p.)-induced accumulation of t-MH and this effect was antagonized by naloxone. A specific inhibitor of histidine decarboxylase, alpha-fluoromethylhistidine (alpha-FMH) (50 mg/kg, i.p.), decreased the brain HA level in consequence of the almost complete depletion of the HA pool with a rapid turnover. Morphine further decreased the brain HA level in alpha-FMH-pretreated mice. Morphine administered alone significantly reduced the HA level in the spinal cord, an area where the turnover of HA is very slow. These results suggest that the acute morphine treatment increases the turnover of neuronal HA via opioid receptors, and this opiate also releases HA from a slowly turning over pool(s).
Insights
Acute morphine treatment increases histamine turnover in the brain via opioid receptors. Morphine also releases histamine from slow-turnover pools in the brain and spinal cord.
Area of Science:
- Neuroscience
- Pharmacology
- Neurochemistry
Background:
- Histamine (HA) plays a role in central nervous system functions.
- Opioid receptors are involved in modulating neurotransmitter systems.
- The interaction between morphine and histamine pathways requires further elucidation.
Purpose of the Study:
- To investigate the impact of acute morphine administration on histamine levels and turnover.
- To explore the influence of morphine on different histamine pools within the brain and spinal cord.
Main Methods:
- Mice were treated with varying doses of morphine sulfate.
- Levels of histamine (HA) and its metabolite tele-methylhistamine (t-MH) were measured.
- Inhibitors of histamine synthesis (alpha-fluoromethylhistidine) and monoamine oxidase (pargyline) were used.
- Naloxone was employed to assess the role of opioid receptors.
Main Results:
- Morphine alone did not alter steady-state brain histamine levels but enhanced pargyline-induced t-MH accumulation, indicating increased HA turnover.
- This effect was reversed by naloxone, confirming involvement of opioid receptors.
- Morphine decreased brain HA levels in mice pretreated with alpha-fluoromethylhistidine, suggesting an effect on HA synthesis or release.
- In the spinal cord, morphine significantly reduced HA levels, where HA turnover is slow.
Conclusions:
- Acute morphine treatment increases the turnover of neuronal histamine in the brain through opioid receptor activation.
- Morphine also appears to release histamine from slowly turning over pools in both the brain and spinal cord.