Establishment of an intestinal injury non-human primate model of methamphetamine-dependent in Rhesus monkeys

Objective To establish an intestinal injury animal model of methamphetamine-dependent in Rhesus monkeys by weekly increasing the dose of methamphetamine. Methods 5 adult Rhesus monkeys which weighed 8-10 kg, 1 for each group. All treated monkeys were injected through vain with methamphetamine twice per day at the beginning concentration of 0.1 mg/kg every time, with 0.05 mg/kg increasing every week. Group A1 was control which was killed at 12 weeks; group A2 was another control which was killed at 24 weeks; group B1 was treated for 12 weeks; group B2 was treated for 12 weeks, and then maintained the last concentration without increasing to 24 weeks; group B3 was treated for 24 weeks. Animals were treated 5 days per week, weighed and phlebotomize every two weeks. Intestinal injury markers was tested by enzyme linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) stain was used to analyze intestinal tissue pathological changes. Results The control groups had little significant change in weight, while the treated groups were off 2.5%-4.8% at 8 weeks, and markedly decreasing of 7.6%-10.8% from 12 weeks. B1-B3 had respectively 7.6%, 25.6%, 33.3% weight off. In treated groups, the blood levels of DAO ascended of 17.5%-29.2% at 10 weeks, of 152.4%-188.4% at 12 weeks, and 27.32, 49.69 U/ml of B2 and B3 separately at the end of 24 weeks. The levels of D-LA rose of 200.0%-220.7% at 12 weeks, constantly rose to 28.47, 38.36 μg/ml of B2 and B3 separately to 24 weeks, which showed the same trends of LPS in group B2 and B3 to 33.70, 46.12 pg/ml separately. Histological results showed inflammatory infiltrate in control groups, while the treated groups, had varying degrees of epithelia erosion, glandular destroyed or disappeared in mucosa lamina propria, degeneration and necrosis of intestinal villus. The thickness of intestinal wall changed in accordance with epithelia erosion. Conclusion The intestinal injury markers, intestinal histologic features and other phenotype of the methamphetamine-dependent animal model were in accordance with intestinal injury, which showed the animal model was successfully established. Key words: Intestinal injury; Model, animal; Methamphetamine; Rhesus monkeys