Systemic morphine produce antinociception mediated by spinal 5-HT7, but not 5-HT1A and 5-HT2 receptors in the spinal cord.
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BACKGROUND AND PURPOSE: The serotonergic system within the spinal cord have been proposed to play an important role in the analgesic effects of systemic morphine. Currently, seven groups of 5-HT receptors (5-HT1-7) have been characterized. One of the most recently identified subtypes of 5 HT receptor is the 5-HT7 receptor. We aimed to examine the role of spinal 5-HT7 receptors in the antinociceptive effects of systemic morphine. EXPERIMENTAL APPROACH: The involvement of spinal 5-HT7 receptor in systemic morphine antinociception was compared to that of the 5-HT1A and 5-HT2 receptors by using the selective 5-HT7 receptor antagonist, SB-269970, the selective 5-HT1A receptor antagonist, WAY 100635, the selective 5-HT2 antagonist ketanserin as well as the non-selective 5-HT1,2,7 receptor antagonist, metergoline. Nociception was evaluated by the radiant heat tail-flick test. KEY RESULTS: I.t. administration of SB-269970 (10 microg) and metergoline (20 microg) completely blocked the s.c. administered morphine-induced (1, 3, 5 and 10 mg kg(-1)) antinociception in a time-dependent manner. Additionally, i.t. administration of SB-269970 (1, 3, 10 and 20 microg) and metergoline (1, 5, 10 and 20 microg) dose dependently inhibited the antinociceptive effects of a maximal dose of morphine (10 mg kg(-1), s.c.). I.t. administration of WAY 100635 (20 microg) or ketanserine (20 microg) did not alter morphine-induced (1, 3, 5 and 10 mg kg(-1), s.c.) antinociception. CONCLUSION AND IMPLICATIONS: These findings indicate that the involvement of spinal 5-HT7, but not of 5-HT1A or of 5-HT2 receptors in the antinociceptive effects of systemic morphine. (+info)
cis-Urocanic acid stimulates primary human keratinocytes independently of serotonin or platelet-activating factor receptors.
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Serotonin mediated changes in corticotropin releasing factor mRNA expression and feeding behavior isolated to the hypothalamic paraventricular nuclei.
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The 5-HT1 receptor agonist RU-24969 decreases 5-hydroxytryptamine (5-HT) release and metabolism in the rat frontal cortex in vitro and in vivo.
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K+-stimulated release of [3H]-5-hydroxytryptamine ( [3H]-5-HT) from rat frontal cortex slices was decreased by the 5-HT receptor agonists 5-methoxy-n1N-dimethyltryptamine and 5-methoxy-3(1,2,3,6,-tetrahydro-4-pyrindinyl)-1H-indole (RU-24969) (1 X 10(-5)M). RU-24969 (10 mg kg-1, i.p.) decreased extracellular 5-HT and its metabolite 5-hydroxyindoleacetic acid measured in vivo by use of intracerebral dialysis combined with high performance liquid chromatography and electrochemical detection. The decrease in extracellular 5-hydroxyindoleacetic acid in vivo after RU-24969 (10 mg kg-1, i.p.) was also observed by in vivo voltammetry. The non-selective 5-HT antagonist metergoline prevented the RU-24969-induced decrease in 5-HT release and metabolism in vivo while the 5-HT2 receptor antagonist R-55669 (ritanserin) did not. The results support the view that RU-24969 stimulates a 5-HT1 receptor that is involved in the autoregulation of 5-HT release and metabolism. (+info)
5-Hydroxytryptamine release in vivo from a cytoplasmic pool: studies on the 5-HT behavioural syndrome in reserpinized rats.
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Treatment of rats with reserpine in order to disrupt vesicular amine storage reduces 5-hydroxytryptamine (5-HT) levels throughout brain by 90-95%. Despite the drastic reduction in brain 5-HT content by reserpine, the 5-HT releasing drug p-chloramphetamine (PCA) produces a behavioural syndrome in reserpine-treated rats which is not different from that observed in normal animals given PCA. Prior treatment of reserpinized rats with p-chlorophenylalanine (PCPA), the irreversible tryptophan hydroxylase inhibitor which inhibits the synthesis of new 5-HT, prevents the PCA-induced behavioural syndrome. The 5-HT receptor antagonist methergoline, blocks the PCA effect in reserpine-treated rats. Treatment of reserpinized rats with pargyline, a non-selective inhibitor of monoamine oxidase, in order to increase cerebral 5-HT levels, shifts the PCA dose-response curve for inducing the 5-HT behavioural syndrome to the left. The specific 5-HT uptake blocker, fluoxetine, protects normal and reserpine-treated rats from the 5-HT depleting effects of PCA but does not always prevent the PCA-induced 5-HT behavioural syndrome. These results indicate that PCA releases 5-HT into the synapse from a small cytoplasmic pool which is resistant to reserpine and suggest that this newly synthesized compartment of 5-HT represents the 'functional' transmitter pool. (+info)
The effect of selective 5-hydroxytryptamine uptake inhibitors on 5-methoxy-N,N-dimethyltryptamine-induced ejaculation in the rat.
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The ejaculatory response and the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1 i.p.) were studied following acute and repeated treatment of rats with the selective uptake inhibitors of 5-HT, fluoxetine, zimeldine, alaproclate, and citalopram. The oral doses used were based on the respective ED50 values for uptake inhibition. Acute doses of fluoxetine and zimeldine significantly reduced the ejaculatory response when given 48 h before 5-MeODMT. This blockade was prevented by treatment of the rats with the postsynaptic 5-HT receptor antagonist methergoline. An acute dose of fluoxetine given 7 and 14 days before 5-MeODMT significantly enhanced the ejaculatory response. On day 24, the response returned to the control level. Repeated treatment every second day (5 times over 9 days and 10 times over 19 days) with fluoxetine caused a longer blockade of the ejaculatory response and the sensitization of the response came later than after an acute dose. Parallel with the ejaculatory response three other components of the 5-HT behavioural syndrome also decreased significantly. Acute doses of alaproclate and citalopram significantly blocked the ejaculatory response at 1 h, but they failed to affect the response at any other time point after either acute or repeated treatment. Neither did these drugs attentuate the 5-HT syndrome. It is concluded that acute and repeated treatment of rats with different selective 5-HT uptake inhibitors does not produce a common alteration in 5-HT2-receptor functions. (+info)
Metergoline in the inhibition of puerperal lactation.
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Seventy-eight mothers who did not want to breast-feed their newborn infants took part in a trial to assess whether metergoline could effectively suppress puerperal lactation. Metergoline 8 mg/day was given to 69 women within 24 hours after delivery and continued for five days to prevent lactation. The remaining nine women were given a course of metergoline once lactation had started. The drug was effective in both preventing and suppressing lactation. Milk secretion, engorgement, and pain were significantly reduced in women taking metergoline. Metergoline has a similar effect to bromocriptine in suppressing lactation, but its mechanism of action remains unknown. (+info)