Changed concentrations of tachykinins and neuropeptide Y in brain of a ratmodel of depression: Lithium treatment normalizes tachykinins

Lithium's therapeutic mechanism of action is unknown. In lithium-treated no rmal rats, increased striatal concentrations of neurokinin A (NKA)-like imm unoreactivity (LI), substance P (SP-LI) and neuropeptide Y (NPY-LI) have be en reported. To investigate whether these effects might be of therapeutic r elevance, Flinders Sensitive Line rats (FSL), an animal model of depression , and control Flinders Resistant Line (FRL) rats were during a 6-week perio d fed chow to which either lithium or vehicle was admixed. Following sacrif ice, the peptides were extracted from dissected brain regions and measured by radioimmunoassay. NKA-LI and SP-LI were markedly decreased in striatum a nd increased in frontal cortex in FSL compared to control FRL animals. Lith ium treatment abolished these differences. Basal concentrations of NPY-LI w ere decreased in hippocampus of FSL rats, but unaffected by lithium. The pr esent study suggests that changed tachykinins and NPY may underlie the char acterized depressive-like phenotype of the FSL rats. It is hypothesized tha t altering tachykinin peptidergic neurotransmission in striatum and frontal cortex constitutes a mechanism of action of lithium and that such a mechan ism might be of therapeutic relevance. [Neuropsychopharmacology 24:183-191, 2001] (C) 2000 American College of Neuropsychopharmacology. Published by E lsevier Science Inc.