Abstract:
:Alterations in serotonin (5-hydroxytriptamine, 5-HT), norepinephrine, and gamma-aminobutyric acid have been linked to the pathophysiology of anxiety and depression, and medications that modulate these neurotransmitters are widely used to treat mood disorders. Recently, the neuropeptide substance P (SP) and its receptor, the neurokinin 1 receptor (NK1R), have been proposed as possible targets for new antidepressant and anxiolytic therapies. However, animal and human studies have so far failed to provide a clear consensus on the role of SP in the modulation of emotional states. Here we show that both genetic disruption and acute pharmacological blockade of the NK1R in mice result in a marked reduction of anxiety and stress-related responses. These behavioral changes are paralleled by an increase in the firing rate of 5-HT neurons in the dorsal raphe nucleus, a major source of serotonergic input to the forebrain. NK1R disruption also results in a selective desensitization of 5-HT1A inhibitory autoreceptors, which resembles the effect of sustained antidepressant treatment. Together these results indicate that the SP system powerfully modulates anxiety and suggest that this effect is at least in part mediated by changes in the 5-HT system.
journal_name
Proc Natl Acad Sci U S Aauthors
Santarelli L,Gobbi G,Debs PC,Sibille ET,Blier P,Hen R,Heath MJdoi
10.1073/pnas.041596398keywords:
subject
Has Abstractpub_date
2001-02-13 00:00:00pages
1912-7issue
4eissn
0027-8424issn
1091-6490pii
041596398journal_volume
98pub_type
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