Abstract
The neuropeptide PACAP is widely distributed in the nervous system and implicated in neurotransmission, neural plasticity, and neurotrophic actions. PACAP is structurally highly conserved during evolution, implying its vital importance. In Drosophila, loss-of-function mutations in a PACAP-like neuropeptide gene, amnesiac, result in impairment of memory retention and increased sensitivity to ethanol. There is a parallel between memory formation in Drosophila and mammals: PACAP-deficient (PACAP−/−) mice and PACAP-specific (PAC1) receptor-deficient mice show impaired memory performance and hippocampal long-term potentiation (LTP). In contrast to that in Drosophila, PACAP−/− mice had a reduced sensitivity to hypnotic effect of ethanol. However, in both cases, PACAP or amnesiac products are likely to play significant roles in both memory formation and modifying the intoxicating effects of ethanol. We additionally showed that PACAP−/− mice display altered psychomotor behaviors, including hyperkinesia, impaired habituation, and anorexia, and manifest in a deficit in sensorimotor gating in a development-dependent manner. Theses observations suggest that PACAP−/− mice are relevant to investigating the development and neural substrate of human psychopathologies. Thus, by these genomics-based approaches, we have demonstrated the implication of PACAP in higher brain functions including memory formation and psychological processes. [Jpn J Physiol 55 Suppl:S33 (2005)]
