Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function

• DOI: 10.1073/pnas.98.4.1912
• Publication Date: 2012-07-26T23:12:10Z
• Authors: Luca Santarelli; Gabriella Gobbi; Pierre C. Debs; Etienne L. Sibille; Pierre Blier; René Hen; Mark J. S. Heath
• Keywords: Dorsal raphe nucleus; Forebrain

Alterations in serotonin (5-hydroxytriptamine, 5-HT), norepinephrine, and gamma-aminobutyric acid have been linked to the pathophysiology of anxiety depression, medications that modulate these neurotransmitters are widely used treat mood disorders. Recently, neuropeptide substance P (SP) its receptor, neurokinin 1 receptor (NK1R), proposed as possible targets for new antidepressant anxiolytic therapies. However, animal human studies so far failed provide a clear consensus on role SP modulation emotional states. Here we show both genetic disruption acute pharmacological blockade NK1R mice result marked reduction stress-related responses. These behavioral changes paralleled by an increase firing rate 5-HT neurons dorsal raphe nucleus, major source serotonergic input forebrain. also results selective desensitization 5-HT1A inhibitory autoreceptors, which resembles effect sustained treatment. Together indicate system powerfully modulates suggest this is at least part mediated system.