Changed concentrations of tachykinins and neuropeptide Y in brain of a rat model of depression: lithium treatment normalizes tachykinins.
Lithium's therapeutic mechanism of action is unknown. In lithium-treated normal rats, increased striatal concentrations of neurokinin A (NKA)-like immunoreactivity (LI), substance P (SP-LI) and neuropeptide Y (NPY-LI) have been reported. To investigate whether these effects might be of therapeutic relevance, Flinders Sensitive Line rats (FSL), an animal model of depression, and control Flinders Resistant Line (FRL) rats were during a 6-week period fed chow to which either lithium or vehicle was admixed. Following sacrifice, the peptides were extracted from dissected brain regions and measured by radioimmunoassay. NKA-LI and SP-LI were markedly decreased in striatum and increased in frontal cortex in FSL compared to control FRL animals. Lithium treatment abolished these differences. Basal concentrations of NPY-LI were decreased in hippocampus of FSL rats, but unaffected by lithium. The present study suggests that changed tachykinins and NPY may underlie the characterized depressive-like phenotype of the FSL rats. It is hypothesized that altering tachykinin peptidergic neurotransmission in striatum and frontal cortex constitutes a mechanism of action of lithium and that such a mechanism might be of therapeutic relevance.
Husum
H
H
Institution of Clinical Neuroscience, Karolinska Institutet, St. Görans Hospital, SE-11281, Stockholm, Sweden.
Vasquez
P A
PA
Mathé
A A
AA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D018021:Lithium Chloride / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009478:Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity; D015320:Tachykinins / Q000187:drug effects / Q000378:metabolism*
D009478:Neuropeptide Y; D015320:Tachykinins; D018021:Lithium Chloride