PREFERENTIAL INDUCTION BY STRESS OF THE N-METHYL-D-ASPARTATE RECOGNITION DOMAIN IN DISCRETE STRUCTURES OF RAT-BRAIN

Immobilization stress in water for 3 h was effective in inducing signi ficant potentiation of [H-3] (+)-5-methyl-10,11-dihydro- 5H-dibenzo [a ,d] cyclohepten-5,10-imine ([H-3] MK-801) binding 5 days after the str essful manipulation in rat hypothalamus and cerebellum when determined before equilibrium in the absence of any added agonists, in addition to resulting in marked reduction of rearing behaviors of animals. Howe ver, the stressful manipulation failed to modulate the [H-3] MK-801 bi nding in other central regions examined, and binding of either [H-3] l pha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid or [H-3]kainic acid was not significantly affected in all brain structures studied 5 days after the stress application. In contrast, the stressful procedur es potentiated binding of both L-[H-3]glutamic ([H-3]Glu) and o-4-prop yl-5-phosphono-3-pentenoic([H-3]CGP-39653) acids in the hypothalamus a nd cerebellum 5 days later, without affecting binding of [H-3]-glycine and 5,7-dichloro[H-3]kynurenic acid. The systemic administration of c orticosterone mimicked the stress manipulation at doses of 5-50 mg/kg in terms of inducing significant enhancement of binding of both [H-3]G lu and [H-3]CGP-39653 in the hypothalamus and cerebellum when determin ed 5 days after the single administration. The translation inhibitor c ycloheximide was effective in preventing the stress-induced potentiati on of [H-3]Glu binding in the cerebellum, without altering thatcerebel lum, without altering that in the hypothalamus. Furthermore, the stres sful handling significantly increased the densities of [H-3]Glu bindin g sites in the hypothalamus and cerebellum, with the affinities being unchanged. These results suggest that stress may preferentially potent iate binding of radioligands to the N-methyl-D-aspartate recognition d omain through facilitation of de novo biosynthesis in rat hypothalamus and cerebellum.