Effects of age and gender on the expression of brain-derived neurotrophic factor mRNA in rat retrosplenial cortex following administration of dizocilpine

Using in situ hybridization, we studied the effects of age and gender on th e expression of brain-derived neurotrophic factor (BDNF) mRNA and heat shoc k protein hsp-70 mRNA in the rat retrosplenial cortex following administrat ion of the noncompetitive NMDA receptor antagonist (+)-MK-801 (dizocilpine) . Male and female Sprague-Dawley rats (5 weeks, 12 weeks, or 10 months old) were given a single intraperitoneal injection of saline (1 ml/kg) or dizoc ilpine (0.3, 1.0, or 3.0 mg/kg). No expression of BDNF mRNA and hsp-70 mRNA was detected in the rat retrosplenial cortex after administration of salin e (1 ml/kg, IP). Administration of dizocilpine (0.3, 1.0, or 3.0 mg/kg, IP) caused a marked induction of BDNF mRNA and hsp-70 mRNA in the retrosplenia l cortex of male and female rats, in a dose-dependent manner. Female rats w ere more sensitive to the induction of BDNF mRNA and hsp-70 mRNA in the ret rosplenial cortex by dizocilpine as compared to male rats. It was also foun d that adult (12 weeks old) and aged (10 months old) rats were more sensiti ve to the induction of hsp-70 mRNA and BDNF mRNA in the retrosplenial corte x by dizocilpine as compared to young (5 weeks old) rats. These results sug gest that the age and gender differences observed in the expression of BDNF mRNA and hsp-70 mRNA in the retrosplenial cortex by dizocilpine may be ass ociated with the differences in dizocilpine-induced neurotoxicity observed with gender and age within the same region. [Neuropsychopharmacology 25:258 -266, 2001] (C) 2001 American College of Neuropsychology. Published by Else vier Science Inc.