Expressão genômica de receptores serotonérgicos e de neuropeptídeos na matéria cinzenta periaquedutal dorsal de ratos submetidos ao isolamento social neonatal e adulto

Abstract

The defensive responses to electrical stimulation of dorsal periaqueductal gray matter (DPAG) have been proposed as a model of panic attacks. In turn, clinical and epidemiological studies suggest that childhood separation anxiety (CSA) predisposes individuals to the development of both panic and depression. The molecular basis of these effects are nevertheless completely unknown. Accordingly, here we evaluated the DPAG 5HT levels and the expression of 5-HT1A and 5-HT2A serotonin receptors and the neuropeptides FosB, substance P (SP) and brain-derived neurotrophic factor (BDNF) in adult rats which were subjected to two models of CSA, namely, 3-h daily neonatal social isolation (NSI) from postnatal days 2 to 21 (PN2-PN21) and 24-h maternal deprivation (MD) at PN9. Controls were puppies briefly manipulated for 15 s (BH) or those bred without manipulation. The effects of maternal care were also examined in adult rats reunited to mothers either conscious (CM) or anesthetized (AM) when neonates. As adults (PN60), rats were evaluated in anxiety and depression tests and sacrificed for DPAG collection for biochemical (HPLC) and genomic (rt-PCR) analysis. The effects of neonatal isolation were further compared to those of the adult social isolation (ASI) for 1 (ASI-1) or 7 (ASI-7) days. While adult weight was reduced mainly in NSI, an anhedonia was observed only in MD (AM or CM) and BH-AM (NSI and MD). Anxiety was reduced in the NSI group. Although expression of 5-HT1A, 5-HT2A, SP, FosB and BDNF did not change, 5-HT levels increased markedly in DPAG of NSI and BH groups. In contrast, the ASI produced significant increase in both SP (ASI-1 and ASI-7 groups) and BDNF (ISA-7 group). These results suggest that DPAG increased expression of SP and BDNF is a marker of ASI only.