Methamphetamine protects against stress-induced gastric mucosal lesions in mice

Department of Medical Toxicology, Kawasaki Medical School, Kurashiki, Japan.
Legal Medicine (Impact Factor: 1.24). 03/2009; 11 Suppl 1:S437-9. DOI: 10.1016/j.legalmed.2009.01.020
Source: PubMed


Stress-induced gastric mucosal injury is a common clinical entity. On the other hand, abuse of methamphetamine (MA) represents a growing social problem. MA users are frequently in stressful situations. In this study, we examined the effects of MA on gastric injury, corticosterone level and immunomodulation using a water-immersion restraint stress (WRS) mouse model that is well known to induce gastric lesions. Mice were randomly divided into five groups: (1) the normal group, (2) the 3 hour (3 h)-WRS group, (3) the 6 hour (6 h)-WRS group, (4) the MA (3 mg/kg) plus 6 h-WRS group and (5) the MA (30 mg/kg) plus 6h-WRS group. As expected, most animals examined (above 90%) showed gastric injury after the WRS exposure. However, administration of MA at both 3 and 30 mg/kg resulted in significant suppression of the injury. The corticosterone levels were increased by exposure to the stress and/or MA, but there was no difference between these groups. The levels of the serum cytokines IL-6, IL-10 and TNF were increased by WRS, and were markedly increased by MA plus WRS; in particular, the level of IL-6 was synergistically increased. On the contrary, the level of IL-1beta was significantly decreased by WRS and MA plus WRS. This is the first report showing the protective effect of MA on stress-induced gastric injury, although further study is necessary to resolve the mechanism of MA-driven suppression of the injury.

17 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effects of acute systemic administration of duloxetine, amitriptyline, mirtazapine and fluoxetine were compared in experimental models of gastric ulcer in rats. Compared with the vehicle control group, duloxetine (5, 10 and 20 mg/kg, i.p.), amitriptyline (10 and 20 mg/kg, i.p.), mirtazapine (10 and 20 mg/kg, i.p.) and fluoxetine (5 and 10 mg/kg, i.p.) significantly protected against water-immersion plus restraint stress-induced gastric lesions, as evidenced by dose-dependent decrease in ulcer index and score for intraluminal bleeding. Duloxetine (20 mg/kg, i.p.), amitriptyline (10 and 20 mg/kg, i.p.), fluoxetine (10 and 20 mg/kg, i.p.) and mirtazapine (5, 10 and 20 mg/kg, i.p.) significantly decreased indomethacin (30 mg/kg, i.p.)-induced gastric lesions and intraluminal bleeding. In reserpine (25 mg/kg, i.p.)-induced gastric ulcer experiment, duloxetine (5, 10 and 20 mg/kg, i.p.), amitriptyline (5, 10 and 20 mg/kg, i.p.), fluoxetine (10 mg/kg, i.p.) and mirtazapine (5 mg/kg, i.p.) significantly attenuated gastric lesions and intraluminal bleeding. These results (a) highlighted the relationship in correlating antiulcer effect of drugs from different antidepressant classes across various animal gastric ulcer models and (b) suggested that antidepressants that differently affected both norepinephrine and serotonin levels (such as duloxetine, amitriptyline and mirtazapine) had more potent and efficacious antiulcer effect in various gastric ulcer animal models than drugs that only affected serotonin level (such as fluoxetine).
    European journal of pharmacology 07/2012; 691(1-3):46-51. DOI:10.1016/j.ejphar.2012.06.041 · 2.53 Impact Factor