PACAP/PAC1シグナルによる青斑核ノルアドレナリン神経制御機序の解明

• Published in: 日本薬理学会年会要旨集 p. 4-B-P-300
• Main Authors: THU, NGUYEN THI, 栗原, 崇, 神戸, 悠輝, 宮田, 篤郎
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: behavior; neuropeptide; noradrenaline (norepinephrine)
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_4-B-P-300

Both pituitary adenylate cyclase-activating polypeptides (PACAP) and noradrenaline are known to be involved in anxiety and fear memory. However, the crosstalk of these substances has not been clarified previously. Here we investigated the PACAP action in the locus coeruleus (LC) noradrenergic system based on the mice. To evaluate the significance of PACAP on the mice behavior, we used the PACAP-knockout (-/-) mice.PACAP (-/-) mice less stayed in the open arm of the elevated plus maze than wild-type (WT) mice, suggesting PACAP has an anxiogenic effect. When a fear conditioning test was conducted using PACAP (-/-) mice, the freezing time was significantly decreased compared to WT mice suggesting that PACAP is important for fear memory formation.PAC1 is PACAP-specific receptor. To examine whether PAC1 was expressed in LC noradrenergic neurons, we observed coexistence of tyrosine hydroxylase immunoreactivity and PAC1 mRNA, revealing expression of PAC1 in the LC noradrenergic neurons. To examine whether PAC1 functional expressed in the LC, we measured extracellular noradrenaline in the hippocampus after PACAP treatment. Intracerebroventricular injection of PACAP increased hippocampal noradrenaline, suggesting PACAP/PAC1 signaling in the LC is active. From the results show above,  PACAP/PAC1 signaling might activate LC noradrenergic system. In the future, we will clarify the significance of LC PACAP/PAC1 signaling on mice behavior.