Adolescent development influences functional responsiveness of noradrenergic projections to the hypothalamus in male...

Hypothalamic noradrenergic utilization in vivo and the in vitro depolarized release of norepinephrine (NE) were measured at 28, 42, and 70 days of age in male rats to determine the impact of adolescent development on the functional responsiveness of this transmitter system. At each age, function was determined in control rats and rats challenged by restraint. NE utilization in vivo was estimated by measuring the decrease in NE levels following administration of a synthesis inhibitor, alpha-methyl-p-tyrosine methyl ester (alpha-MT, 250 mg/kg). The half-life of approach to a new steady-state was determined. To measure depolarized release of NE, the hypothalamus was incubated in vitro in a high potassium (50 mM) medium and the percent of endogenous NE released into the medium was determined. The in vivo results indicated that hypothalamic NE utilization in control animals decreases as animals mature. Additionally, the in vitro results indicated that the percent NE released upon depolarization also decreased with maturation in control animals. Restraint shifted the NE decay curve measured in vivo to the right at all ages. Overall, however, restraint tended to increase NE utilization at 70 days, have little effect at 42 days, and retard utilization at 28 days. Furthermore, restraint markedly reduced the depolarized release of NE at 28 days, had no effect at 42 days and slightly, but significantly, increased release at 70 days. Restraint significantly increased plasma corticosterone at all ages. Hypothalamic NE projections are important to an organism's regulatory responses, and changes that take place over adolescence in this system may be important for the emergence of adult-typical responses as well as render adolescents vulnerable to specific dysfunctions.