Verificação dos efeitos de imipramina, paroxetina, buspirona e diazepam no labirinto em T elevado em ratos e camundongos

Abstract

The disorders of anxiety use to have high levels of prevalence among population, with varying degrees of severity, eventually causing disability. Deakin & Graeff have conceived a theoretical model, relating distal defence, amygdala and generalized anxiety, on the one hand, and proximal defence, periaqueductal grey substance and panic, on the other. In this proposal, serotonin eases anxiety, but inhibits the panic. The format of the Elevated T Maze (ETM) would be more effective to distinguish these two patterns of anxiety, in contrast to Elevated plus maze (EPM), one of the models most frequently used to evaluate anxiolytic effects of drugs. The model was validated for rats, with little description about the use in mice. In the first experiment, the animals (Swiss mice, 10 in each group) were treated with saline (10 ml / kg, ip), imipramine (30mg/kg; ip), diazepan (1mg/kg; ip), paroxetine (5mg/kg ; Ip), paroxetine (10mg/kg; ip) and paroxetine (20mg/kg; ip) and evaluated in the Forced Swim Test (FST). In the second experiment the mice were divided into five groups (n = 10) and treated with saline (10 ml/kg, ip), imipramine (30mg/kg; ip), diazepan (2mg/kg; ip), paroxetine (10mg / kg, ip), buspirone (10mg/kg; ip), daily for one week (subchronic), and after that they were evaluated in the FST. In the third experiment mice were treated subcronic with saline, imipramine (30mg/kg; IP), paroxetine (10mg/kg; IP), diazepam (2mg/kg; IP) and buspirone (10mg/kg; IP) and then tested in EPM. In the fourth experiment, were used Wistar rats that received daily, by gavage, saline, imipramine (10mg/kg), paroxetine (10mg/kg), diazepam (1mg/kg) or buspirone (10mg/kg) for 24 consecutive days (in volume 1 ml per kg) and then were evaluated in ETM and Open Field Test (OFT). The fifth experiment was similar to the fourth, being used mice and adapted device for ETM. The results were: imipramine and three doses of paroxetine presented antidepressant effect, as diazepam showed depressive effect on acute FST. In subchronic FST, only imipramine presented antidepressant effect. In the EPM, imipramine presented anxiolytic effect as paroxetine presented anxiogenic effect. In ETM with rats chronically treated, paroxetine, diazepan and buspirone showed anti-generalized-anxiety-like effect, as imipramine, diazepan and paroxetine showed anti-panic-like effect. In ETM with mice chronically treated with imipramine, diazepan, buspirone and paroxetine presented responses anti-generalized-anxiety-like and only paroxetine showed anti-panic-like effect. Thus, imipramine, a drug effective in depressive disorders, generalized anxiety and panic, was responsible for similar responses in animal models (except for the ETM for mice). Diazepam, a drug used to generalized anxiety and with some effects in panic, presented similar behavior in the models, with antipanic-like effect in ETM for rats and not for the mice. Buspirone, a drug used in clinic only to generalized anxiety, did not present antidepressant or antipanic effects in any experiment. Paroxetine, a selective serotonin reuptake inhibitor (SSRI), antidepressant, anxiolytic and antipanic, presented anxiogenic activity in EPM (demonstrating this device as inadequate to evaluate this class of drugs) and anti-generalized-anxiety and anti-panic both in ETM for rats and for mice. We concludes that the ETM for mice is an appropriate model to detect anxiolytic and anti-panic effects of drugs, the latter especially for 5-HT drugs.