Age-related modification of dopaminergic and β-adrenergic receptor system: Restoration to normal activity by modifying membrane fluidity with s-adenosylmethionine

1. Effects of substances which are able to alter brain histamine levels on the nociceptive threshold were investigated in mice and rats by means of tests inducing three different kinds of noxious stimuli: mechanical (paw pressure), chemical (abdominal constriction) and thermal (hot plate). 2. A wide range of i.c.v. doses of histamine 2HCl was studied. Relatively high dose were dose-dependently antinociceptive in all three tests: 5-100 micrograms per rat in the paw pressure test, 5-50 micrograms per mouse in the abdominal constriction test and 50-100 micrograms per mouse in the hot plate test. Conversely, very low doses were hyperalgesic: 0.5 microgram per rat in the paw pressure test and 0.1-1 microgram per mouse in the hot plate test. In the abdominal constriction test no hyperalgesic effect was observed. 3. The histamine H3 antagonist, thioperamide maleate, elicited a weak but statistically significant dose-dependent antinociceptive effect by both parenteral (10-40 mg kg-1) and i.c.v. (1.1-10 micrograms per rat and 3.4-10 micrograms per mouse) routes. 4. The histamine H3 agonist, (R)-alpha-methylhistamine dihydrogenomaleate was hyperalgesic, with a rapid effect (15 min after treatment) following i.c.v. administration of 1 microgram per rat and 3 microgram per mouse, or i.p. administration of 100 mg kg-1 in mice. In rats 20 mg kg-1, i.p. elicited hyperalgesia only 4 h after treatment. 5. Thioperamide-induced antinociception was completely prevented by pretreatment with a non-hyperalgesic i.p. dose of (R)-alpha-methylhistamine in the mouse hot plate and abdominal constriction tests. Antagonism was also observed when both substances were administered i.c.v. in rats. 6. L-Histidine HCl dose-dependently induced a slowly occurring antinociception in all three tests. The doses of 250 and 500 mg kg-1, i.p. were effective in the rat paw pressure test, and those of 500 and 1500 mg kg-1, i.p. in the mouse hot plate test. In the mouse abdominal constriction test 500 and 1000 mg kg-1, i.p. showed their maximum effect 2 h after treatment. 7. The histamine N-methyltransferase inhibitor, metoprine, elicited a long-lasting, dose-dependent antinociception in all three tests by both i.p. (10-30 mg kg-1) and i.c.v. (50-100 micrograms per rat) routes. 8. To ascertain the mechanism of action of the antinociceptive effect of L-histidine and metoprine, the two substances were also studied in combination with the histamine synthesis inhibitor (S)-alpha-fluoromethylhistidine and with (R)-alpha-methylhistamine, respectively. L-Histidine antinociception was completely antagonized in all three tests by pretreatment with (S)-alpha-fluoromethylhistidine HCl (50 mg kg-1, i.p.)administered 2 h before L-histidine treatment. Similarly, metoprine antinociception was prevented by(R)-alpha-methylhistamine dihydrogenomaleate 20 mg kg-1, i.p. administered 15 min before metoprine. Both(S)-alpha-fluoromethylhistidine and (R)-alpha-methylhistamine were used at doses which did not modify the nociceptive threshold when given alone.9. The catabolism product, 1-methylhistamine, administered i.c.v. had no effect in either rat paw pressure or mouse abdominal constriction tests.10. These results indicate that the antinociceptive action of histamine may take place on the postsynaptic site, and that its hyperalgesic effect occurs with low doses acting on the presynaptic receptor. This hypothesis is supported by the fact that the H3 antagonist, thioperamide is antinociceptive and the H3 agonist, (R)-alpha-methylhistamine is hyperalgesic, probably modulating endogenous histamine release.L-Histidine and metoprine, which are both able to increase brain histamine levels, are also able to induce antinociception in mice and rats. Involvement of the histaminergic system in the modulation of nociceptive stimuli is thus proposed.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1994.tb14883.x

Role of histamine in rodent antinociception.

Endogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting

Morphine is most effective on gastrointestinal propulsion in rats by intraperitoneal route: Evidence for local action

Neurotensin (NT), a tridecapeptide originally isolated from the hypothalamus, exhibits a wide variety of biological effects which depend on the site of peptide administration. The systemic and central effects of NT on GH, PRL, and TSH secretion were compared in urethane anesthetized, estrogen-primed male rats.ntravenous NT (30 /xg/kg or 7.5–9.0 /xg/rat) produced a marked rise in plasma GH and PRL, which peaked at 5 rnin, and in plasma TSH, which peaked at 15 min. In contrast, intraventricular (ivt) NT (2 and 5 /ig) significantly decreased plasma levels of all three hormones. The PRL and TSH rises after systemic TRH (0.4 /ig/ kg) were inhibited by the ivt injection of NT (0.2 and 2.0 jug). The GH rise after chlorpromazine (200 jug/kg, iv) was completely suppressed by NT (0.5 and 0.2 jug, ivt), whereas that of PRL was partially suppressed. To evaluate the possible mediation of NT effects by substance P, somatostatin, and histamine, the pituitary hormon responses to these compounds were measured. The injecti...

Dissociation of Systemic and Central Effects of Neurotensin on the Secretion of Growth Hormone, Prolactin, and Thyrotropin*

A simple and inexpensive cannula technique for chemical stimulation of the brain

Forty rats, maintained on either ad lib food and water or on 22-h food deprivation, were tested in a photobeam cage under conditions of no specific external stimulation or where tone, light, or the odor of amyl acetate or food were presented. The results indicated that the onset of all stimuli resulted in an increase in activity counts for all groups, but the increment in activity varied for the different stimuli. The greatest increase in activity for the ad lib group was to the light stimulus; for the food-deprived group, it was to the food-odor stimulus.

/pdf/the-effect-of-the-onset-of-stimuli-on-reactivity-in-the-rat-24gskuihmp.pdf

The effect of the onset of stimuli on reactivity in the rat

Three rats with cannulae implanted in the posterior hypothalamic area and one nonimplant rat were tested in a conditioned suppression paradigm. During the acquisition phase of conditioned suppression, xylocaine hydrochloride was administered bilaterally via cannulae to two of the implant animals and an equal volume of normal saline was administered to the third animal. The xylocaine-injected animals required approximately twice the number of CS-UCS pairings as the saline-injected animal and five times the number of CS-UCS pairings as the normal control animal to acquire conditioned suppression. The maintenance of conditioned suppression was generally unaffected by xylocaine lesions.

/pdf/the-effect-of-reversible-lesions-in-the-posterior-145ptsibav.pdf

Paul D’encarnacao

Papers

A simple and inexpensive cannula technique for chemical stimulation of the brain

The effect of the onset of stimuli on reactivity in the rat

The effect of reversible lesions in the posterior hypothalamus on conditioned suppression