the effect on GR expression is apparent only after 4 days of treatment, a seemingly obscure fact whose importance will later become evidence. The effect of 5-CT on GR expression is blocked by methiothepin. Likewise, 5-CT produces a significant increase in cAMP levels and the effect is blocked by methiothepin. Pindolol, which binds to the 5-HT1A, but not the 5-HT7 receptor, has little effect (see also reference 76). These results further implicate the 5-HT7 receptor. The intracellular effects of cAMP are commonly mediated by cyclic nucleotide-dependent protein kinases (PKA) and, predictably, a PKA inhibitor (H8) blocks the effects of 5HT or cAMP on hippocampal GR expression. Over the course of these studies, we found that other serotonergic agonists (quipazine, TFMPP [1-(trifluoromethylphenyl) piperazine], and DOI [(+/-)-2,5-demethoxy-4-iodoamphetamine]) could partially mimic the 5-HT effect on GR levels and, in all studies, the magnitude of the serotonergic effect on cAMP concentrations is highly correlated (r=0.97) with that on GR expression.78 This observation is consistent with the idea that the effect of 5-HT on GR expression in hippocampal neurons is mediated by a 5-HT7 receptor via activation of cAMP Importantly, both postnatal handling and increased maternal LG increase hippocampal concentrations of both cAMP and PKA
