Efeitos agudos e crônicos da fluoxetina em modelos experimentais de pânico, ansiedade e depressão em ratos adultos submetidos ao isolamento social neonatal

• Autor(a) principal: Bernabé, Cristie Setubal
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/7987
• topic: Matéria cinzenta periaquedutal; Pânico; Isolamento social neonatal; Fluoxetina; Fisiologia; 612

Clinical studies suggest that childhood separation anxiety (CSA) predisposes panic attacks (PA). In turn, neonatal social isolation (NSI) and the defensive behaviors produced by electrical stimulation of the dorsal periaqueductal gray matter (DPAG) were proposed as the rat analogues of CSA and PA, respectively. Indeed, recent evidence from our laboratory showed that NSI facilitates DPAG-evoked panic-like behaviors in adult rats under seven days of social isolation. On the other hand, epidemiologic studies show that only a genetic liability set during childhood contributes to the development of panic in the presence of environmental stressful events experienced into adulthood. Because the serotonin-selective reuptake inhibitors (SSRIs) are the first-line treatment of panic disorder, here we examined the effects of 21-day intraperitoneal administrations of either fluoxetine (FLX 1 and 2mg/kg/day), saline (SAL) or untreated (FIC) on anxiety-, depression- and panic-like responses of NSI adult rats. Also, we reduced the stressful condition of social isolation by grouping the rats after the electrode implantation surgery procedure to test the influence of housing on PA in NSI adult rats. The NSI was carried out by placing the entire litter separated from its mother for 3 hours dally throughout the lactation period (post-natal day 2-21, PN2- PN21). Separated pups (P, n=83) were placed in individual boxes while the dam was moved to a different box in a novel room while the controls (NP, n=80) remained with their mother and were submitted to the same manipulation protocol of P pups. Both groups were divided into FIC, SAL, FLX1 and FLX2 treatments. Rats were implanted with electrodes in the DPAG at PN52 and electrically stimulated at PN59 (screening session), PN60 (acute effects) and PN67, PN74 and PN81 (chronic effects). Rat behaviors were also assessed for anxiety in the elevated-plus-maze (PN82) and open field (PN83), and for anhedonia and depression in sucrose intake test (PN78- 81) and forced swimming test (PN84), respectively. Our data showed that the P group had depressive-like behaviors as compared to NP (p<0.001) and FLX was able to reverse this effect (p<0.01). All treatments of the P group had an increase of up to 60% of the defensive thresholds (I50) throughout the stimulation sessions (p<0,001) and a decrease of these (I50 up to -15,4%, p<0,001) as compared to NP. In NP group, only FLX2 was able to increase the defensive thresholds of the DPAG (I50= up to 70%, p<0,0001). The depressive-like behaviors assessed on the present study corroborate with previous reports and show an antidepressive-like behavior produced by FLX treatment in NSI rats. Additionally, although with a less pronounced effect, the reduction of the defensive behaviors of the P group as compared to NP agrees with early reports from our laboratory. While the median rates of the P rats had no differences due to the different treatments, only FLX2 was able to increase the defensive thresholds on NP group. Interestingly, the gradual increase of the medians in all treatments of the P group throughout the stimulation sessions suggests a similar motivational deficit behavior observed on depressed rats submitted to the learned helplessness paradigm.