Biomedical subjects

N H Majeed

Publications and source records attributed to N H Majeed.

11 recordsLinked to original sources

PubMed1994

Inhibition of nitric oxide synthase attenuates the development of morphine tolerance and dependence in mice.

The effect of the nitric oxide (NO) synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 5-20 mg/kg i.p.) and NG-nitro-L-arginine (NO2Arg, 5-20 mg/kg i.p.) on morphine-induced analgesia, as well as on morphine induced tolerance and dependence was examined in male albino Swiss mice. Neither acute nor repeated (for 5 days) administration of the nitric oxide synthase inhibitor, L-NAME affected the morphine induced analgesia, as measured by hot plate and tail-flick tests. On the other hand, administration of L-NAME or NO2Arg along with morphine prevented the development of tolerance to the analgesic effect of morphine for at least 7 days, whereas the analgesic effect of morphine alone disappeared after 5 days. L-NAME and NO2Arg also attenuated some signs of morphine dependence, as assessed by naloxone (2 mg/kg)-precipitated withdrawal. These results indicate that NO may play a role in the development of morphine tolerance and dependence.

Amino Acid Oxidoreductases↗

PubMed1991

Stimulation of food intake in rats by the alpha 2-adrenoceptor agonists xylazine and detomidine.

Effects of the alpha 2-adrenoceptor agonists xylazine and detomidine on food intake in freely feeding male rats were evaluated. Intraperitoneal (i.p.) injection of xylazine (0.25-3 mg/kg) and detomidine (25 and 50 micrograms/kg) significantly increased the 2 and 24 h food intake from control values. Treatment of rats with the alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg, i.p.) 15 min before xylazine (0.5 mg/kg, i.p.) or detomidine (50 micrograms/kg, i.p.) significantly inhibited the increase in food intake. Yohimbine treatments alone at 0.5, 1 and 2 mg/kg, i.p. did not significantly change the 2 and 24 h food intake from control values. The results suggest that the alpha 2-agonists xylazine and detomidine enhance food intake in rats.

Adrenergic alpha-Agonists↗

PubMed1987

The in vitro release of immunoreactive dynorphin and alpha-neoendorphin from the perfused rat duodenum.

The release of immunoreactive (ir) dynorphin (DYN) and alpha-neoendorphin (ir-ANEO) from the isolated perfused rat duodenum was demonstrated using specific radioimmunoassays (RIAs). Depolarization of the tissue by increasing the potassium (K+) concentration up to 108 mM enhanced the release of ir-DYN and ir-ANEO in Ca2+-dependent manner. Administration of the serotonin-releasing agent fenfluramine (10(-6) M) and the serotonin receptor agonist m-chlorophenylpiperazine (m-CPP, 10(-6) M) stimulated the release of ir-DYN and ir-ANEO from the duodenum. A subsequent study revealed that serotonin (5-HT, 10(-6)-10(-4) M) induced a dose-dependent increase in the release of ir-DYN and ir-ANEO from the duodenum. The effect of 5-HT on the release of ir-DYN and ir-ANEO from the duodenum was antagonized by 5-HT antagonist cyproheptadine (10(-6) M). The presence of dynorphin and the related peptides in the gastrointestinal tract (GIT) and their release from the duodenum in vitro indicate that these peptides may act as transmitters involved in some GIT functions. Furthermore, our results suggest that at least part of 5-HT effects on the GIT may be mediated by the release of dynorphin and the related peptides.

Animals↗

PubMed1986

Involvement of endogenous opioid peptides in fenfluramine anorexia.

The effect of chronic fenfluramine (20 mg/kg, once daily) injections on the brain and peripheral immunoreactive (ir) dynorphin (DYN), alpha-neoendorphin (ANEO) and beta-endorphin (BE) was studied in rats. Fenfluramine injected repeatedly for 5 and 9 days induced anorexia. In the same animals there were no significant changes in the ir-DYN and ir-ANEO contents in the brain and pituitary. However, the ir-DYN and ir-ANEO contents in the gastrointestinal tract (duodenum) were markedly decreased after 5 and 9 days of fenfluramine injection. In contrast to ir-DYN and ir-ANEO, there was an increase in the hypothalamic and a decrease in the anterior lobe of pituitary ir-BE content. There was no significant change in the neurointermediate (NI) lobe of the pituitary. The results of our study suggest that part of the fenfluramine anorexia may be mediated by the peripheral prodynorphin and central beta-endorphin systems.

Animals↗

PubMed1986

Brain and peripheral opioid peptides after changes in ingestive behavior.

The levels of dynorphin, alpha-neoendorphin and beta-endorphin immunoreactivity (ir-DYN, ir-alpha-NEO, ir-beta-E) were measured in the brain, pituitary and gut of rats subjected to a variety of manipulations. Water deprivation caused an increase in the ir-DYN and ir-alpha-NEO content in the hypothalamus and a decrease in the neurointermediate (NI) lobe of the pituitary. The ir-beta-E level decreased in the hypothalamus and anterior lobe of the pituitary, while it increased in the NI-pituitary. Food deprivation, as well as chronic fenfluramine (10-20 mg/kg) treatment increased, while acute muscimol (0.5 micrograms/10 microliter) treatment decreased the ir-beta-E, but not ir-DYN or ir-alpha-NEO content in the hypothalamus. The anterior pituitary content of ir-beta-E was increased after food deprivation and decreased after chronic fenfluramine treatment. However, the ir-DYN and ir-alpha-NEO contents in the duodenum were markedly increased after food deprivation, while chronic fenfluramine treatment led to a dramatic decrease in the ir-DYN content. These results suggest that the levels of opioid peptides in the brain, pituitary and gut may be differentially and independently affected by alteration of the ingestive behavior.

Animals↗

PubMed1985

Differential regulation of the brain and gut immunoreactive dynorphin by the serotonin system.

Administration of drugs such as fenfluramine, 20-40 mg/kg, and m-chlorophenylpiperazine (m-CPP), 2.5-5 mg/kg, which release serotonin or activate postsynaptic serotonin receptors, respectively, induced a dramatic decrease in the duodenal content of immunoreactive dynorphin (ir-DYN). The effect was antagonized by cyproheptadine, 1 mg/kg. Similarly, acute administration of the specific serotonin reuptake blockers fluvoxamine, 15 mg/kg, or femoxetine, 10 mg/kg, and 5-hydroxytryptophan (5-HTP), 40-160 mg/kg, evoked a marked decrease in the duodenal content of ir-DYN. A combined administration of fluvoxamine or femoxetine and 5-HTP failed to potentiate the effect of individual treatment. Only a higher dose of fenfluramine, 40 mg/kg, increased the ir-DYN content in the hypothalamus. These results suggest that the brain and gut ir-DYN is independently regulated by the serotonin system and that a serotonin mechanism might stimulate release of the gut dynorphin content.

5-Hydroxytryptophan↗

PubMed1985

Differential modulation of the beta-endorphin and dynorphin systems by serotonergic stimulation in the rat.

The serotonergic modulation of the brain, pituitary and gut beta-endorphin and dynorphin systems in the rat was determined pharmacologically. Acute administration of fenfluramine (20 mg/kg), m-chlorophenylpiperazine (m-CPP 2.5 mg/kg), fluvoxamine (15 mg/kg) and 5-hydroxytryptophan (5-HTP 160 mg/kg) increased immunoreactive (ir)beta-endorphin (beta E) in the hypothalamus and decreased it in the anterior lobe of the pituitary. That effect was antagonized by cyproheptadine (1 mg/kg). None of the treatments altered significantly ir-dynorphin (DYN) level in the hypothalamus and pituitary, however, ir-DYN in the gut was dramatically decreased after fenfluramine, m-CPP, fluvoxamine, femoxetine and 5-HTP, the latter effects being antagonized by cyproheptadine. The obtained results suggest that the serotonin system might stimulate the release of the anterior pituitary beta-endorphin and gut dynorphin pools, while the brain beta-endorphin system appears to be inhibited by activation of serotonin neurons.

Animals↗

PubMed1985

Antidepressants and endogenous opioid peptide systems.

The influence of antidepressants on the brain and pituitary content of immunoreactive beta-endorphin (ir-beta E) and dynorphin (ir-DYN) was studied in rats. Chronic administration of the first and second generation antidepressants imipramine, citalopram and rolipram, and of the antidepressant neuroleptics levomepromazine and chlorprothixene elevated the level of ir-beta E in the hypothalamus. Imipramine and levomepromazine also increased the level of ir-DYN in this tissue. Imipramine administered chronically potentiated stress-induced as well as morphine analgesia. The results obtained suggest that chronic antidepressants enhance the brain opioid system activity and increase the sensitivity of opiate receptors.

Animals↗

PubMedDate not supplied

Stimulation of food intake following opioid microinjection into the nucleus accumbens septi in rats.

The involvement of opioid peptides in the regulation of food intake has been postulated. However, it is not known how they are involved in this regulation and which brain region is responsible for the mediation of their effects. We studied the effect of a microinjection of opioid agonists and antagonists into the nucleus accumbens septi (NAS) on the food intake in rats, as this area is known to be important for motivation. Male Wistar rats were implanted stereotaxically with guide cannulae. Rats were not allowed food prior to drug treatment and solutions (1 microliter) were microinjected bilaterally. Food intake was measured throughout a 2 hr period after the drug injection. Infusions into the NAS of 2, 5 and 10 nmol of morphine, D-ala2, D-Leu5-enkephalin (DADLE), and beta-endorphin (beta E), or of 5 and 10 nmol of alpha-neoendorphin (ANEO) induced a dose-dependent increase in the food intake. Dynorphin (DYN) also increased the food intake, but only at a 10 nmol dose. The new, highly selective delta agonist D-Pen2,5-enkephalin (DPDPE) induced a dose-dependent increase in the food intake. Naloxone in doses of 2 and 10 nmol antagonized the increased food intake induced by morphine, beta E, ANEO and DYN in a dose-dependent manner, but only partly antagonized the effect of DADLE on the food intake. The selective mu-receptor antagonist beta-funaltrexamine (beta-FNA), in a dose of 5 nmol completely blocked the increase in the food intake induced by morphine but not by DADLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Serotonergic regulation of the brain and gut beta-endorphin and dynorphin content in the rat.

A specific radioimmunoassay was used to measure immunoreactive dynorphin (ir-DYN) and beta-endorphin (ir-BE) in the brain, pituitary and gut, following a pharmacological manipulation of the serotonin system. Administration of the serotonin receptor agonist m-chlorophenylpiperazine (m-CPP, 2.5-5 mg/kg ip) or the serotonin releasing agent fenfluramine (20-40 mg/kg ip) induced a significant increase in the hypothalamic ir-BE content and a decrease in its anterior pituitary level. These effects were antagonized by cyproheptadine (1 mg/kg ip). Similar results were obtained after fluvoxamine (15 mg/kg ip), femoxetine (10 mg/kg ip) and 5-hydroxytryptophan (5-HTP 40-160 mg/kg ip). None of the above treatments altered significantly the ir-DYN content in the brain and pituitary. However, the gut ir-DYN level was dramatically decreased after m-CPP, fenfluramine, fluvoxamine, femoxetine and 5-HTP. The latter effect was antagonized by cyproheptadine. The obtained results suggest that serotonergic activation stimulates the release of beta-endorphin from the anterior pituitary and dynorphin from the gut, while the cerebral beta-endorphin system appears to be inhibited by activation of serotonin neurons.

Animals↗

PubMedDate not supplied

Degradation of the labelled beta-endorphin is an important factor of direct RIA in the human and rat plasma.

Degradation of iodinated beta-endorphin in human and rat plasma was investigated, using different proteinase inhibitors. This degradation affects the radioimmunoassay quality. Additional blank tubes were also prepared during assay procedure to avoid the effect of 125-I-beta-endorphin adsorption on the dextran-coated charcoal in the presence and absence of plasma proteins, what avoids underestimation of the beta-endorphin level in plasma samples. Based on the above observations, the sensitive and direct radioimmunoassay of beta-endorphin was developed in human and rat plasma.

Animals↗