The 5-HT7 receptor is positively coupled to adenylyl cyclase, and thus the activation of cAMP In vivo, both handling and increased maternal LG result in an increased level of hippocampal cAMP concentrations and the activation of PKA over the first week of postnatal life.76 Activation of PKA results in the tissue-specific induction of a number of transcription factors. The day6 offspring of high-LG mothers or pups of the same age exposed to handling show increased hippocampal expression of NGFIA (nerve growth factor-induced clone A, also known as zif-268, krox-24, egr-1, and zenk) (Weaver IGC et al, unpublished results).79 In vitro, 5-HT increases NGFIA expression in cultured hippocampal neurons and the effect of 5-HT on GR expression in hippocampal cultures is completely blocked by concurrent treatment with an oligonucleotide antisense directed at the NGFIA mRNA.80 The antisense is a synthetic strand of nucleotides that hybridizes with the native mRNA and prevents transcription of the NGFIA protein. These studies serve to identify a relevant transcription factor and to link the activation of the transcription factor NGFIA to the activation of GR expression in response to 5-HT.
