L-ephedrine-induced neuro degeneration in the parietal cortex and thalamusof the rat is dependent on hyperthermia and can be altered by the process of in vivo brain microdialysis

Multiple doses of the dietary supplement L-ephedrine can cause severe hyper thermia, and modest dopamine depletions in the rat brain. Since D-amphetami ne treatment can result in neurodegeneration, the potential of L-ephedrine to produce similar types of degeneration was investigated. Adult male rats, some implanted in the caudate/putamen (CPu) for microdialysis, were given four doses of 25 mg/kg L-ephedrine or 5 mg/kg D-amphetamine (2 h between do ses) at an ambient temperature of 23 degreesC. L-ephedrine-induced degenera tion in the forebrain was dependent on the degree of hyperthermia. Layer IV of the parietal cortex was the most Sensitive to L-ephedrine treatment wit h peak body temperatures of at most 40.0 degreesC necessary to produce dege neration. Extensive neurodegeneration in the parietal cortex after L-ephedr ine treatment was as pronounced as that previously described for D-amphetam ine treatment and also occurred in the intralaminar, ventromedial and ventr olateral thalamic nuclei in rats with severe hyperthermia (peak body temper atures>41.0 degreesC). The neurodegeneration induced by L-ephedrine may hav e resulted in part from excitotoxic mechanisms involving the indirect pathw ays of the basal ganglia and related areas. No differences were observed be tween microdialysis and non-implanted rats with respect to degree of tyrosi ne hydroxylase (TH) loss in the CPu after either D-amphetamine or L-ephedri ne treatment. However, neuro degeneration resulting from D-amphetamine and L-ephedrine was reduced in the microdialysis animals in the hemisphere ipsi lateral to the probe, which raises concerns when using the technique of in vivo microdialysis to evaluate neurodegeneration. The results of this study , in conjunction with human clinical evaluation of ephedrine neurotoxicity, indicate that regionally specific damage may occur in the cortex of some h umans exposed to ephedrine in the absence of stroke or hemorrhage. (C) 2001 Published by Elsevier Science Ireland Ltd.