Female rats are more sensitive to the locomotor alterations following quinolinic acid-induced striatal lesions: Effects of striatal transplants

Abstract

The effects of sex differences and hormonal factors on the locomotor alterations following intrastriatal injections of quinolinic acid (QA) and the ability of fetal striatal transplants to reverse those effects were examined. Male, female, or ovariectomized female rats received bilateral injections of 150 nmol QA or vehicle into the striatum. Using a multidimensional analysis of spontaneous nocturnal locomotor behavior, a significant increase in locomotion was observed in female but not male or ovariectomized female rats. The increases in activity observed in the lesioned females were attenuated at 6 and 10 weeks following transplantation of rat fetal (E17) striatal tissue into the lesioned striata. Transplanted striatal tissue had no effect on locomotion in male or ovariectomized female rats. Cytochrome oxidase histochemistry revealed that QA produced a marked loss of metabolic activity in regions exhibiting cell loss. Within these areas there was a marked loss of striatal neurons including those reactive for NADPH diaphorase. Despite the sex-related differences in QA-induced locomotion, there were no apparent differences in the extent of striatal pathology or survival of the grafts in any of the groups receiving QA. These experiments demonstrate a sex-dependent dissociation between the behavioral and neurobiological consequences of QA and suggest that sex and hormonal variables play an important role in the locomotor changes following excitotoxic-induced striatal damage.