The modulatory role of neurokinins in affective behaviors

Abstract

Neurokinins are peptide molecules with modulatory actions on other neurotransmitter systems, notably the monoaminergic ones, within the CNS and peripheral tissues. A great deal of evidence supports a role for these substances, mainly for substance P and its main receptor NK1 , in a number of physiologic and pathologic conditions, including affective and behavioral responses to stress. NK1 receptor antagonists have shown preclinical activity in several paradigms of anxiety and depression. Mutant mice lacking the NK1 receptor gene have an increased firing rate of dorsal raphe serotonergic neurons, an effect that can also be seen after the administration of substance P antagonists. When given chronically, NK1 antagonists promote an enhancement of serotonergic transmission in the hippocampus that seems to be mediated by interaction with other neurotransmission systems. Clinical efficacy of such drugs has also been demonstrated among patients with major depression, although the results have been inconclusive. More research is needed to elucidate the precise role these drugs could play in the treatment of affective disorders in the future.