Nociception, a pain response mechanism, occurs in response to stimuli that threaten the integrity of an organism. The first synapses produced as a result of the initiation of nociception are modulated by excitatory amino acids (glutamate and aspartate) and many peptides (substance P, CGRP, CCK, endogenous opioids). Nociceptin (also designated orphanin FQ) is a neuronal peptide that is similar to opioid peptides. Nociceptin activates KOR-3 (kappa-type opioid receptor, also designated ORL1), a G protein-coupled receptor. Although similar to dynorphin A, a kappa opioid peptide, nociceptin functions to make animals hyperreactive to nociceptive stimulations. Nociceptin is also involved in locomotor behavior and may be involved in the modulation of synaptic plasticity in learning and memory.