Cold acclimation and central administration of homocysteic acid in rats: a potential model for schizophrenia

Abstract

Homocysteic acid (HCA) is a neurotoxin and a NMDA receptor agonist that is taken up in GABAergic interneurons by the cystine/glutamate exchanger, System xc‐, and then slowly released. We thus hypothesized that HCA may trigger a slowly developing neurodegeneration of GABAergic interneurons, which might serve as a model for schizophrenia. In addition, we hypothesized that cold acclimation would exacerbate the effects of the HCA. In this study, HCA was injected bilaterally into the lateral cerebral ventricles of rats. Two days later half of the rats were placed in a 5°C environmental chamber. Behavioral testing for motor performance, anxiety, social interaction, hedonistic behavior, and spatial learning and memory began three weeks later. Cold acclimation reduced body weight gain, motor performance and exploratory behavior while HCA decreased exploratory behavior. Neither cold acclimation nor HCA altered spatial learning or memory or social interaction. Both cold acclimation and HCA altered hedonistic behavior as measured with a saccharine preference test. There were no significant interactions between cold acclimation and HCA for any behavioral test. These results indicate that both central administration of HCA and cold acclimation can alter performance in behavioral tests that may relate to schizophrenia‐like behavior in rats but cold acclimation does not potentiate the effects of HCA.