CONTROL OF ENDOGENOUS NOREPINEPHRINE RELEASE IN THE HYPOTHALAMUS OF MALE-RATS CHANGES OVER ADOLESCENT DEVELOPMENT

In order to evaluate mechanisms that could contribute to the effect of adolescent development on the in vivo utilization of norepinephrine ( NE) in the hypothalamus, the depolarized release of endogenous norepin ephrine (using 50 mM potassium) was measured in vitro in hypothalamic explants from male rats over late juvenile (28 days) to young adult (7 0 days) ages. Depolarized release, expressed as a percent of the total endogenous pool, was significantly greater in juveniles than in eithe r adolescents (42 days) or young adults, Incubation in the presence of idazoxan, an alpha(2)-adrenoceptor antagonist, increased the depolari zed fractional NE release in adolescent and young adult rats; however, the same drug decreased depolarized release in juveniles. Inhibition of norepinephrine reuptake by incubation in the presence of nisoxetine (1 mu M) significantly increased depolarized release (fractional and absolute) in young adults only. A higher concentration of nisoxetine ( 5 mu M) significantly increased depolarized release in juveniles, but significantly reduced release in adults. Nisoxetine did not influence release in adolescents at either concentration. The possibilities that adolescent development brings about a change in alpha(2)-adrenorecept or subtype and that juveniles may have a greater NE reuptake capacity than adults are discussed. Hypothalamic NE projections are important t o several regulatory functions, and changes that take place in this sy stem over adolescence may be important for the emergence of adult-typi cal responses as well as render adolescents vulnerable to specific dys functions.