Effect of lithium on tachykinins, calcitonin gene-related peptide, and neuropeptide Y in rat brain

Publisher Website
Google Scholar
Abstract
The effects of lithium on brain regional concentrations of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivities (-LI) were studied in rat. In the pilot study, rats were divided into three groups that were administered vehicle, or 1 or 4 mEq/kg lithium sulphate, respectively, intraperitoneally once/day for 9 days. In the second experiment, rats were divided into three groups receiving vehicle, or 1 or 2 mEq/kg lithium sulphate, respectively, intraperitoneally twice/day for 9 days. After sacrifice by focused microwave irradiation, brains were dissected, weighed, and frozen. Peptides were extracted and measured in extract aliquots by specific radioimmunoassays. Marked regional differences (P<.001) were found for each of the peptides measured. In the pilot study the higher lithium dose, 4 mEq/kg, significantly raised neuropeptide levels. However, animals receiving this dose also showed signs of toxicity. In the second experiment, lithium increased SP-LI concentrations in striatum and hypothalamus (72 and 29%, P's<.001 and .05). NKA-LI was also elevated in striatum (44%, P<.01). CGRP-LI, in parallel to SP-LI, was increased in striatum and hypothalamus (58 and 78%, P's <.05 and .01). In contrast, lithium decreased CGRP-LI in the pituitary gland (56%, P < .01). NPY-LI was increased in striatum, and frontal and occipital cortex (30, 66, and 60%, respectively; P's < .01, .01, and .05). In conclusion, lithium, in doses equivalent to those used clinically, has a significant effect on SP-, NKA-, CGRP-, and NPY-LI concentrations in several brain structures, most prominently in the striatum. These findings raise the possibility that lithium's effects on neuropeptides are specific and may represent one of its mechanisms of action on mood and motor behavior.