Efeitos tardios do isolamento social neonatal e do desamparo aprendido sobre os níveis tissulares e taxa de renovação da serotonina das regiões dorsal e ventrolateral da matéria cinzenta periaquedutal de ratos

Abstract

In rats, electrical stimulations of the dorsal half of the periaqueductal gray matter (DPAG) produce freezing and flight behaviors and marked autonomic changes that have been proposed to model panic attacks. Contrarily, stimulations of the ventral half of the PAG (VLPAG) inhibit these behaviors. On the other hand, although the clinical and epidemiological studies suggest that panic is favored by both the childhood separation anxiety (CSA) and depression and/or trauma, recent data from our laboratory showed that the neonatal social isolation (NSI) model of CSA facilitates the DPAG-evoked panic behaviors of adult rats, whereas the learned helplessness (LH) model of depression produces a long-lasting inhibition of these behaviors. Thus, because the serotonergic agents are the first-choice treatment of both panic and depression, here we examined the tissue levels of both serotonin (5-HT) and its main metabolite (5-HIAA), and the 5-HT turnover (5-HT/5-HIAA) of dorsal and ventrolateral PAG. Briefly, rats were subjected to either a 3-h NSI throughout the lactation period or a shuttle-box one-way escape yoked training with footshocks either escapable (ES) or inescapable (IS). Rats were sacrificed 7 and 30 days following the terminus of LH and NSI procedures, respectively. Samples were then collected through punching of 1 mm-thick coronal sections and prepared for HPLC assays. Data of LH and NSI groups were compared to respective histochemical assays of naïve rats (NV). LH data showed that whereas the rats exposed to escapable shocks presented significant increases in the 5-HT levels of the DPAG, those exposed to inescapable shocks did it for the VLPAG. Thus, although the corresponding increases in 5-HT turnover did not reach a statistically significant level, the lack of changes in 5-HIAA levels suggests that 5-HT level increases were due to an augmented synthesis of the neurotransmitter in both the DPAG and VLPAG of escapable and inescapable shock groups, respectively. Contrarily, 5-HT levels and turnover were similarly increased in NSI and control siblings as compared to the NV group. Concluding, the present data suggest that the 5-HT is involved in the late consequences of the LH, but not of the NSI, on DPAG-evoked defensive behaviors.