ADOLESCENT DEVELOPMENT INFLUENCES FUNCTIONAL RESPONSIVENESS OF NORADRENERGIC PROJECTIONS TO THE HYPOTHALAMUS IN MALE-RATS

Hypothalamic noradrenergic utilization In vivo and the in vitro depola rized release of norepinephrine (NE) were measured at 28, 42, and 70 d ays of age in male rats to determine the Impact of adolescent developm ent on the functional responsiveness of this transmitter system. At ea ch age, function was determined in control rats and rats challenged by restraint. NE utilization in vivo was estimated by measuring the decr ease in NE levels following administration of a synthesis inhibitor, a lpha-methyl-p-tyrosine methyl ester (alpha-MT, 250 mg/kg). The half-li fe of approach to a new steady-state was determined. To measure depola rized release of NE. the hypothalamus was incubated in vitro in a high potassium (50 mM) medium and the percent of endogenous NE released in to the medium was determined. The in vivo results indicated that hypot halamic NE utilization in control animals decreases as animals mature. Additionally, the in vitro results indicated that the percent NE rele ased upon depolarization also decreased with maturation in control ani mals. Restraint shifted the NE decay curve measured in vivo to the rig ht at all ages. Overall, however, restraint tended to increase NE util ization at 70 days, have little effect at 42 days, and retard utilizat ion at 28 days, Furthermore, restraint markedly reduced the depolarize d 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 al all ages. Hypothalamic NE projectio ns are important to an organism's regulatory responses, and changes th at take place over adolescence in this system may be important for the emergence of adult-typical responses as well as render adolescents vu lnerable to specific dysfunctions.