Establishing a rapid animal model of osteoporosis with ovariectomy plus low calcium diet in rats.

The objective of this study was to rapidly develop osteoporotic model animals by combining ovariectomy with a low calcium diet in rats. Thirty, eight-week-old, female, Sprague-Dawley rats were either sham-operated (Sham) or ovariectomized (Ovx) and divided into three groups: Sham, Ovx, and Ovx + low calcium diet. Rats in the Sham and Ovx groups were fed a standard diet containing 1.1% w/w calcium while rats in the Ovx + low calcium diet group were fed a diet containing 0.1% w/w calcium. Serum osteocalcin and bone mineral density (BMD) of the lumbar vertebrae were measured 4 and 8 weeks after surgery. The rats were euthanized 12 weeks after surgery, and the BMD of the right femur and histomorphometry of the femoral neck were assessed at that time. The Ovx + low-calcium diet group had a significantly lower mean BMD of the lumbar vertebra and higher mean serum osteocalcin concentration than the Sham and Ovx groups. Twelve weeks after surgery, rats in the Ovx + low calcium diet group had a significantly lower BMD, smaller Tb.Th and Tb.N, and larger Tb.Sp of the right femoral neck than did rats in the Sham and Ovx groups. These data indicate that a low calcium diet can significantly accelerate bone loss in ovariectomized rats. Combining ovariectomy and a low calcium diet can save considerable time in the creation of osteoporotic model animals.

Nalmefene reverses carfentanil-induced loss of righting reflex and respiratory depression in rats.

Reversing the respiratory depression induced by carfentanil involves intravenous administration of naloxone or naltrexone, but this treatment has disadvantages. Hence, finding a more appropriate treatment to counter the depressive actions of carfentanil is needed. In the present study, with the naloxone as a control, we investigated the efficacy of nalmefene for countering the depressive actions of carfentanil. Rats were treated successively with carfentanil (10 µg/kg, i.v.) and nalmefene (9.4-150.0 µg/kg, i.m.), and the duration of loss of righting reflex (LORR) recorded. Respiratory parameters were measured in free-moving rats using a whole-body plethysmograph after rats were administered carfentanil (20 µg/kg, i.v.) and nalmefene (9.4-150.0 µg/kg, i.m.) sequentially. The parameters of arterial blood gases were also examined. Nalmefene (9.4-150.0 µg/kg, i.m.) treatment dose-dependently decreased the duration of carfentanil-induced LORR. The respiratory rate after 60 min of nalmefene (150.0 µg/kg, i.m.) treatment increased from 34.3 ± 5.3 bursts/min to 117.8 ± 18.9 bursts/min, and enhanced pause decreased from 1.1 ± 0.1 to 0.4 ± 0.1, and was close to those of normal rats. Furthermore, nalmefene (37.5-150.0 µg/kg) treatment could enable the PaO2, SaO2 and PaCO2 to approach normal levels 10 min (15 min after carfentanil injection) or 30 min (25 min after carfentanil injection) after injection. While, a single injection of naloxone (150.0 µg/kg, i.m.) only achieved partial remission of respiratory depression. These data suggest that nalmefene more effectively counters the depressive actions induced by carfentanil and is a more appropriate treatment to antagonize carfentanil toxicity compared with naloxone.

Effects of thienorphine on release of dopamine and noradrenalin: an in vivo microdialysis study in rats.

Thenorphine is a new potent long-acting partial opioid agonist. In present study, the effect of thienorphine on noradrenalin (NA) in the locus coeruleus (LC) and dopamine (DA) and its metabolites in the nucleus acumbens (NAc) and the striatum were examined in freely moving rats during acute and chronic thienorphine treatment followed by naloxone-precipitated withdrawal using the in vivo microdialysis technique. Acute thienorphine (1.0mg/kg, s.c.) treatment had no effect on the level of NA in the LC and the level of DA in the NAc and the striatum. Chronic thienorphine (1.0mg/kg, s.c.) third per day for continued 5 days treatment followed by naloxone-precipitated (5.0mg/kg, i.p.) had not alter the extracellular NA level in the LC and the extracellular level of DA in the NAc and the striatum, but significantly increased the level of DOPAC in the striatum. These changes are thought to reflect a direct effect of thienorphine on release of NA and DA. Thus thienorphine deserves further study as a new treatment for opioid dependence.