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 norepinephrine (using 50 mM potassium) was measured in vitro in hypothalamic explants from male rats over late juvenile (28 days) to young adult (70 days) ages. Depolarized release, expressed as a percent of the total endogenous pool, was significantly greater in juveniles than in either adolescents (42 days) or young adults. Incubation in the presence of idazoxan, an alpha 2-adrenoceptor antagonists, increased the depolarized 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 microM) significantly increased depolarized release (fractional and absolute) in young adults only. A higher concentration of nisoxetine (5 microM) 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 adolescents development brings about a change in alpha 2-adrenoceptor subtype and that juveniles may have a greater NE reuptake capacity than adults are discussed. Hypothalamic NE projections are important to several regulatory functions, and changes that take place in this system over adolescence may be important for the emergence of adult-typical responses as well as render adolescents vulnerable to specific dysfunctions.