The neuropeptide galanin has been shown to have mood-regulating effects, possibly through modification of serotonergic neurotransmission . Galanin reduces the gene expression of the enzyme tryptophan hydroxylase, which is the rate-limiting enzyme in 5-HT biosynthesis. The selective galanin-3 receptor (Gal3-R) antagonist SNAP-37889, 30, (K¡ = 17.4 nM) has shown anxiolytic and antidepressant-like activity in animal models: in the rat forced swim test it was active at 3 and 10mg/kg, p.o., producing effects comparable to fluoxetine . SNAP-398299, 31, (K¡ = 5.33 nM) is a highly water-soluble analog of 30 that produced an anxiolytic-like effect (MED = 1mg/kg, p.o.) in the rat social interaction test.
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