Development of morphine induced tolerance and withdrawal symptoms is attenuated by lamotrigine and magnesium sulfate in mice.

The goal of this study was to evaluate the effects of lamotrigine and magnesium sulfate on morphine induced tolerance and withdrawal symptoms in mice. Different groups of mice were received morphine (30 mg kg(-1), s.c.) or morphine (30 mg kg(-1), s.c.)+lamotrigine (10, 20, 30 or 40 mg kg(-1), i.p.) or morphine (30 mg kg(-1), s.c.) + magnesium sulfate (20, 40 or 60 mg kg(-1), i.p.) or morphine (30 mg kg(-1), s.c.) + [lamotrigine (10 mg kg(-1), i.p.) + magnesium sulfate (20mg kg(-1), i.p.)] daily for 4 days. Tolerance was assessed using hot plate after administration of a test dose of morphine (9 mg kg(-1), i.p.) on fifth day. Withdrawal zsymptoms (Jumping and Rearing) were assessed by administration of naloxone (5 mg kg(-1), i.p.) 2 h after the last dose of morphine in fourth day. It was found that administration of lamotrigine or magnesium sulfate or their combination decreased the morphine induced tolerance and withdrawal symptoms. From these results it is concluded that lamotrigine and magnesium sulfate alone or in combination could prevent the development of morphine tolerance and withdrawal symptoms. Glutamate release inhibitory effect of lamotrigine and its possible mechanism and property of magnesium, blocking the N-Methyl-D-Aspartate (NMDA) receptor calcium channel, is probably its mechanism on preventing morphine induced tolerance and dependence.

Effect of treatment for 6 months with human parathyroid hormone (1-34) peptide in ovariectomized cynomolgus monkeys (Macaca fascicularis).

A potential negative side effect of intermittent parathyroid hormone (PTH) therapy to treat osteoporosis is the loss of cortical bone concomitant with increased cancellous bone mass. We addressed this issue by studying the effects of PTH on whole-body, axial, and appendicular bone mass in an animal model with haversian cortical bone remodeling. Ovariectomized, young adult female cynomolgus monkeys were assigned to placebo (n = 9) or PTH groups (n = 10). The PTH group received 10 microg/kg synthetic human PTH(1-34) peptide by subcutaneous injection, 3 days/week for 6 months, and the placebo group received vehicle. Multiple endpoints of bone mass, strength, and turnover in the axial and appendicular skeleton were assessed, including dual-energy X-ray absorptiometry (DEXA), quantitative computed tomography (qCT), analysis of serum (calcium, phosphorus, alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase) and urinary (calcium and creatinine) biomarkers, histomorphometry, and biomechanical testing. Compared with placebo-treated animals, PTH-treated monkeys had no change in whole-body bone mass, but a 6.7% increase in spinal areal bone mineral density (aBMD) was observed. Cortical bone mass measured by qCT at appendicular sites was not affected by PTH treatment, but there were significant increases in cancellous bone mass in the proximal tibia, and a similar trend in the distal radius. Small, transient increases in serum and urinary calcium were observed, but there were no treatment-related effects on other biochemical endpoints. Increased bone formation rate (BFR/BV) in the midradius and midfemur was accompanied by a nonsignificant increase in midfemur porosity. Increased vertebral cancellous bone volume (BV/TV) was associated with greater trabecular and interstitial thickness with no effect on wall thickness. Increases in bone strength were observed in both axial (vertebral maximum stress and load at fracture) and appendicular (femoral neck fracture load) skeleton. Together, these results indicate that PTH therapy in the cynomolgus monkey results in a net gain of spinal and appendicular cancellous bone mass with no adverse effect on cortical bone.

Analysis of dendritic arbors of native and regenerated ganglion cells in the goldfish retina.

The retinas of adult teleost fish can regenerate following injury, but little is known about the neuronal integration of the visual scene that is performed by the regenerated retina. Using goldfish retinal ganglion cells (RGCs) as the experimental system, an evaluation of dendritic arbor structure and passive electrotonic properties was developed, the aim being to quantitatively test the hypothesis that native and regenerated RGC dendritic arbors have similar structural and modeled electrotonic attributes. Fractal dimension was chosen as the descriptor of RGC dendritic arbor complexity, and the arbors' transfer function magnitudes were estimated using an electrically passive, equivalent-circuit analysis. For both native and regenerated RGCs, arbors qualitatively judged to be simple tended to have lower fractal dimension values than arbors judged to be more complex. All cells had similar cut-off frequencies, and for random stimulation of greater than 25% of an RGC's population of dendritic tips, there was a positive correlation between fractal dimension and transfer function magnitude. Some regenerated RGCs had abnormally long primary dendrites, but neither the distributions of fractal dimension values, nor the estimated transfer function magnitudes, were significantly different between native and regenerated RGCs. The results appear to support the hypothesis that structural and modeled electrotonic attributes of regenerated goldfish RGCs are similar to those of native RGCs, suggesting that regenerated RGCs may restore normal visual function.