A distinct neurochemical profile in WKY rats at baseline and in response to acute stress: implications for animal models of anxiety and depression

Abstract

Wistar–Kyoto (WKY) rats exhibit hyperresponsive neuroendocrine and behavioral responses to stress that exceed normal controls and are especially prone to develop stress-induced depressive disorder. Pharmacological studies indicate altered serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems functioning in WKY rats, yet no attempt has been made to provide a comprehensive assessment of the neurochemical profile for WKY rats as compared to the outbred progenitor controls, Wistar rats. To this end, male, WKY and Wistar rats ( N=6/group) were exposed to an acute forced-swim stress or were left untreated as controls. The prefrontal cortex (PFCtx), striatum, nucleus accumbens (NAS), and amygdala were assayed for levels of NE, DA and 5-HT, as well as major metabolites, by high-pressure liquid chromatography (HPLC) with electrochemical detection. In a separate experiment, designed to assess baseline and stress-induced neuroendocrine activation, male, Wistar and WKY rats ( N=6/group) were exposed to an acute forced-swim stress of 15 min or were left untreated as controls. Animals were killed immediately after the test ( T=0), 30 min after the test ( T=30) or 60 min after the test ( T=60), and control animals were killed immediately after weighing. After decapitation, trunk blood was collected and plasma was isolated by centrifugation and analyzed for corticosterone by immunoassay. The neurochemical results demonstrate distinct patterns of baseline and stress-induced monoamine turnover in WKY rats, including alterations to DA and 5-HT turnovers in prefrontal cortex and nucleus accumbens, two critical brain areas implicated in anxiety, depression and drug reward. The neuroendocrine results indicate that WKY rats exhibited a sustained corticosterone response to acute stress, as compared to Wistar controls. Overall, these data are predicted to be useful for understanding the anxiety- and depressive-like behavioral phenotype exhibited by these animals and for increased understanding of the role genetic background in altering neurochemical function.