Modulation of memory retention by neuropeptide K

Neuropeptide K (NPK) is one of the structures in beta-preprotachykinin which also includes substance P. NPK, a 36 amino acid peptide, contains the sequence of neurokinin A as amino acids 27-36 of its C-terminus. Neurokinin A is also contained separately in the gamma-preprotachykinin precursor. Both NPK (2.5-10 micrograms) and neurokinin A administered intracerebroventricularly after footshock avoidance training in the T-maze enhanced memory retention in CD-1 male mice. Local microinjections of NPK enhanced memory retention when injected into the rostral and caudal portions of the hippocampus (0.25 and 0.50 microgram) and the amygdala (1.0 microgram), but were without effect when injected into the septum and the caudate. The differential effects of NPK on memory retention across brain regions differed from those previously reported for substance P and neuropeptide Y. These studies suggest that NPK, acting through discrete anatomical areas, modulates memory processing. The functional significance of co-localization of neuropeptides with classical neurotransmitters and other transmitter peptides in the same neurons is not well understood, but recent studies have indicated that the neuropeptides modulate the release of the primary transmitter. Since NPK occurs in the same precursor molecule as substance P, NPK may be co-released with the putative neurotransmitter substance P and act with it, in a synergistic manner, to enhance memory processing. These studies provide further evidence that the hippocampus is an anatomical structure involved in memory processing that occurs shortly after training.