Is the opioid system involved in the antinociceptive activity of antidepressants?

Antidepressants induce antinociception. The exact mechanism of this effect is not clear. In this study, induced antinociception by antidepressants (fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram and zimelidine) was tested using the general opioid antagonist, naloxone and the kappa preferring antagonist, Mr2266BS. Antinociceptive activity of antidepressants in mice was assessed using the abdominal constriction assay. Briefly, acetic acid (1) was injected intraperitoneally (ip) and the incidence (writhes) counted for 20 minutes as a criteria for nociception. The decrease of writhes, in drug administered animals compared to control group, was calculated as a percentage of control values and designated protection (as a criteria for antinociceptive activity of the drug). All antidepressants tested demonstrated dose-related antinociception induction. Antinociception induced by fluoxetine, fluvoxamine and sertraline was significantly reduced by naloxone and Mr2266BS. In contrast, paroxetine, citalopram and zimelidine induced antinociception not modified by these two opioid receptor antagonists. These data demonstrate an opioid-like activity for some but not all, antidepressants

Bupropion induces sniffing: a possible dopaminergic mechanism

The effect of bupropion, an antidepressant drug, on sniffing behaviour was examined in rats. Animals treated intraperitoneally (i.p.) with different doses of bupropion (5-40 mg/kg) showed sniffing behaviour in a dose-related manner. Pretreatment of animals (i.p.) with the dopamine antagonists SCH 23390 (0.025-0.1 mg/kg) or sulpiride (12.5-50 mg/kg) decreased the sniffing induced by bupropion. Reserpine pretreatment (2.5 mg/kg, i.p., 18 h) alone and in combination with o~-methyl-p-tyrosine (AMPT; 250 mg/kg, i.p.) also reduced the behaviour produced by the drug. The et-adrenoceptor phenoxybenzamine (5 and 10 mg/kg, i.p.) and the [3-adrenoceptor antagonist propranolol (5 and 10 mg/kg, i.p.) administered 60 rain prior to bupropion did not affect the drug's effect on sniffing. Propranolol alone, however, induced sniffing. The antimuscarinic atropine (5 and 10 mg/kg, i.p.) administered 30 min prior to bupropion increased the bupropion response. Atropine alone induced vigorous sniffing. It is concluded that bupropion induced sniffing through a dopaminergic mechanis

Oxidative stress and the fetotoxicity of alcohol consumption during pregnancy.

Pregnant Quackenbush Special mice were exposed to ethanol under semiacute (3.0 g/kg body weight intragastrically, days 7 to 12 of pregnancy), and chronic conditions (15% ethanol in drinking water for 5 weeks before and during pregnancy) to assess whether embryo-fetotoxic actions of the drug involve oxidative stress effects. Effects were monitored both in the maternal system and embryo. Alcohol compromised the maternal system by increasing the generation of lipid peroxides in the liver. It also decreased glutathione and vitamin E levels, and glutathione peroxidase and superoxide dismutase activities in this organ. Glutathione peroxidase activity in the maternal blood decreased. Only minor alcohol-induced changes occurred in the uterine endometrium, including decreased xanthine oxidase and increased gamma-glutamyl transpeptidase. Similarly, only few changes were induced in day-12 embryos by alcohol. In this case, glutathione content and xanthine oxidase activity decreased while glutathione reductase activity increased following exposure to the chronic regime. With the possible exception of the maternal liver where evidence of oxidative damage was detected, these results do not reflect substantial changes in the antioxidant defences of either the pregnant mouse or embryo. However, the changes may contribute to the growth retarding and other fetotoxic effects of alcohol when they are totalled into the multifactorial actions of the drug