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Increase in the extracellular histamine concentration in the rat striatum by mu-opioid receptor activation
Abstract:
The effects of morphine and selective ligands for mu-, kappa-, and delta-opioid receptors on the extracellular histamine (HA) concentration in the striatum of freely moving rats were examined by in vivo microdialysis. On the day after implantation of the dialysis probe, the HA output per 30-min period was measured using HPLC-fluorometry. Morphine (3.8 mg/kg, s.c.) significantly increased the HA output by approximately 200% 1-3 h after treatment. This effect was completely antagonized by naltrexone (1.6 mg/kg, s.c.). The HA output decreased to a level below 10% of the basal value by 4 h after treatment with (S)-alpha-fluoromethyl-histidine (77 mg/kg, s.c.). In such animals, morphine (3.8 mg/kg, s.c.) had no influence on the HA output. [D-Ala2,MePhe4,Gly(ol)5]Enkephalin (DAGO; 0.2 microgram, i.c.v.), a selective mu-agonist, significantly increased the HA output by approximately 150% 0.5-1.5 h after treatment, and this effect was also completely blocked by naltrexone. A selective kappa-agonist, U-50,488 (3.8 and 7.6 mg/kg, s.c.), and a selective delta-agonist, [D-Pen2,D-Pen5]enkephalin (0.5 and 2 micrograms, i.c.v.), had no effect on the HA output. These findings suggest that the stimulation of mu-opioid receptors by morphine and DAGO increases the extracellular HA concentration by accelerating HA release from nerve endings.
Insights
Morphine and mu-opioid receptor agonists significantly increase extracellular histamine (HA) in rat striatum. This effect is blocked by naltrexone, suggesting mu-opioid receptor involvement in HA release.
Area of Science:
- Neuropharmacology
- Neurochemistry
Background:
- Histamine (HA) plays a role in central nervous system functions.
- Opioid receptors (mu, kappa, delta) modulate various physiological processes.
Purpose of the Study:
- To investigate the effects of morphine and selective opioid receptor agonists on extracellular HA levels in the rat striatum.
- To determine the specific opioid receptor subtypes involved in HA modulation.
Main Methods:
- In vivo microdialysis in freely moving rats.
- High-performance liquid chromatography (HPLC)-fluorometry for HA measurement.
- Administration of morphine, selective opioid agonists (DAGO, U-50,488, D-Pen), and antagonists (naltrexone).
Main Results:
- Morphine (3.8 mg/kg) increased HA output by ~200% 1-3 hours post-treatment, an effect blocked by naltrexone.
- Selective mu-opioid agonist DAGO (0.2 µg, i.c.v.) increased HA output by ~150%, also blocked by naltrexone.
- Selective kappa and delta-opioid agonists did not affect HA output.
- (S)-alpha-fluoromethyl-histidine pretreatment abolished morphine's effect on HA.
Conclusions:
- Stimulation of mu-opioid receptors by morphine and DAGO increases extracellular HA concentrations.
- This increase is mediated by accelerated HA release from nerve endings.
- Kappa and delta-opioid receptors do not appear to influence extracellular HA levels in the striatum.