Expression Of Withdrawal Syndrome Research Articles

Effects of the prenatal exposure to crocin in the expression of withdrawal syndrome on reflexive motor behaviors in mice offspring’s

The aim of the current study was to determine effects of the prenatal exposure to crocin in the expression of withdrawal syndrome on reflexive motor behaviors in mice offspring’s. Fourteen male mice and 56 adult female mice were randomly divided into seven groups as: control group (morphine-abstinent male and female); group 2, drug-naïve female and morphine-abstinent male; group 3, drug-naïve male and morphine-abstinent females; group 4, drug-naïve male and female. Groups 5–7, were similar to groups 2–4, except crocin (5 mg/kg) were injected to drug-naïve subjects. Following delivery, 20 pups from each litter were selected and behavior and reflexive motor behaviors were determined. Also, blood samples were taken to determine serum antioxidant activity. According to the results, immobility time significantly increased in offspring of the paternal + maternal exposed to morphine swimming test and tail suspension tests (P < 0.05) and significantly decreased in offspring of paternal + maternal exposed to morphine + crocin group (P < 0.05). Ambulation, surface righting, hind-limb suspension, grip strength and front limb suspension significantly decreased in offspring of the mice exposed to morphine (P < 0.05) and significantly improved in offspring of paternal + maternal exposed to morphine + crocin group (P < 0.05). Hind-limb foot angle and negative geotaxis significantly increased in mice with morphine-exposed offspring’s (P < 0.05) while improved in offspring of paternal + maternal exposed to morphine + crocin group (P < 0.05). Prenatal exposure to morphine increased Malondialdehyde while decreased Superoxide dismutase, Glutathione peroxidase and total antioxidant status in mice offspring’s (P < 0.05) and these results reversed by prenatal exposure to crocin (P < 0.05). In all studied factors, paternal + maternal exposed to morphine + crocin group had better results compared to the other crocin-received drug-naïve groups (P < 0.05). These results suggested prenatal exposure to crocin decreased morphine-induced adverse effect which paternal and maternal exposed to morphine + crocin had the highest prevention against these effects in mice offspring’s.

The effects of simultaneous administration of alpha(2) -adrenergic agents with L-NAME or L-arginine on the development and expression of morphine dependence in mice.

Both alpha(2)-adrenoceptors and the L-arginine/nitric oxide (NO) pathway have been implicated in the modulation of morphine dependence. This study examined the effects of simultaneous administration of the alpha(2)-adrenoceptor agonist clonidine or the antagonist yohimbine together with the NO precursor L-arginine or the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on the induction and expression of morphine dependence as assessed by naloxone-precipitated withdrawal jumping and diarrhoea. Male NMRI mice weighing 20-30 g were used. In the induction phase, clonidine (0.01-0.1 mg/kg) intensified and yohimbine (0.5-2 mg/kg) attenuated the degree of morphine dependence. Yohimbine reversed the effect of clonidine. L-NAME (5 and 10 mg/kg) did not affect the development of morphine dependence, but significantly potentiated the effects of both subeffective (0.01 mg/kg) and effective (0.03 mg/kg) doses of clonidine. L-Arginine did not alter morphine dependence but inhibited the effect of clonidine. The effects of yohimbine in the induction phase were attenuated by L-NAME, but were not significantly affected by L-arginine. In the expression phase, clonidine attenuated and yohimbine intensified the signs of dependence. The effect of clonidine was inhibited by yohimbine. In the expression phase, L-NAME attenuated the withdrawal syndrome at 10 mg/kg and showed potentiation with clonidine in suppressing withdrawal signs. L-Arginine did not alter morphine dependence, but at 20 mg/kg inhibited and at 100 mg/kg potentiated the attenuating effect of clonidine on the expression of withdrawal syndrome. The effect of yohimbine on the expression phase was also attenuated by L-NAME, but was not significantly affected by L-arginine. In conclusion, alpha(2)-adrenergic and NO pathways seem to be functionally linked in the modulation of opioid dependence.

Further evidence for a role of NMDA receptors in the locus coeruleus in the expression of withdrawal syndrome from opioids

To examine a role of N-methyl- d-aspartate (NMDA) receptors in the locus coeruleus (LC) in the expression of the withdrawal signs from opioids, rats were continuously infused with morphine (a μ-opioid agonist, 26 nmol/μl per h) or butorphanol (a μ/δ/κ-mixed opioid agonist, 26 nmol/μl per h) intracerebroventricularly (i.c.v.) through osmotic minipumps for 3 days. An LC injection of NMDA (0.1 and 1 nmol/5 μl) induced withdrawal signs in opioid-dependent animals. However, it did not precipitate any abnormal behaviors in saline-treated control rats. The expression of the withdrawal signs precipitated by NMDA (1 nmol/5 μl), glutamate (10 nmol/5 μl), or naloxone (an opioid antagonist, 24 nmol/5 μl) was completely blocked by pretreatment with a NMDA antagonist, MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[ a,d]cycloheptan-5,10-imine), 0.1 mg/kg, i.p. In animals that had been infused with opioids in the same manner, naloxone (48 nmol/5 μl, i.c.v.) precipitated withdrawal signs and increased extracellular glutamate levels in the LC of opioid-dependent rats measured by in vivo microdialysis method. Pretreatment with MK-801, however, did not affect the increases of glutamate levels in the LC. These results further demonstrate that the expression of opioid withdrawal induced by an expeditious release of glutamate in the LC region of opioid-dependent animals might be mainly mediated by the postsynaptic NMDA receptors.

Simultaneous measurement of biogenic amines and their metabolites in rat brain regions after acute administration of and abrupt withdrawal from butorphanol or morphine.

Changes in levels of biogenic amines and metabolites were measured using high performance liquid chromatography fitted with an electrochemical detection in various rat brain regions after acute administration of and abrupt withdrawal from continuous intracerebroventricular infusion of butorphanol (a mu/delta/kappa mixed opioid receptor agonist) or morphine (a mu-opioid receptor agonist). A single dose of butorphanol (26 nmol/5 microliters) or morphine (26 nmol/5 microliters) increased levels of 3,4-dihydroxyphenylacetic acid in the striatum and limbic region and of homovanilic acid in the cortex, striatum, and limbic region. In animals which had been infused with butorphanol (26 nmol/microliters/hr) or morphine (26 nmol/microliters/hr) for 3 days, an increase in dopamine turnover was observed. The levels of 3,4-dihydroxyphenylacetic acid was decreased and that of homovanilic acid was increased in the striatum, limbic region, and midbrain immediately after termination of opioid infusion. Both dopamine metabolites (in these areas) were decreased at 2 and 6 hr after butorphanol or morphine withdrawal. Changes in norepinephrine, serotonin, and 5-hydroxyindoleacetic acid levels in some brain regions were observed in the morphine-, but not in butorphanol-dependent rats. These data suggest that the increase and the decrease in dopaminergic activity, but not noradrenergic and serotonergic neurons, in the some brain regions are closely associated with the production of antinociception of and the expression of withdrawal syndrome from butorphanol and morphine, respectively.