Neuropeptide receptors have recently become targets for novel antidepressants. The receptors of the neuropeptide galanin may represent a promising target for the development of putative antidepressants, given galanin’s anatomical localization and role in regulation of homeostatic and motivated behaviors. We have recently shown that treatment with three different antidepressant modalities – electroconvulsive shock, sleep deprivation and SSRI – increase levels of galanin mRNA throughout the rat brain (X. Lu et al., SFN abstract 851.10, 2003). Presently, we determined the effects of two systemically-active, low molecular weight galanin receptor agonists, galnon and galmic, on behavior in preclinical tests of antidepressant activity in rats and mice. Galnon displayed a clear dose-dependent effect in the forced swim test in rats, whereby the two highest doses of the drug (20, 40 mg/kg, i.p.) produced a significant increase in time spent active in the task. Similarly, a dose of galmic (15 mg/kg, i.p.) produced a...