A fixed volume incubation method in conjunction with HPLC-ED analysis was employed to measure endogenous NA release in vitro in slices of hippocampus and hypothalamus from rats reared in either groups of five or in social isolation from weaning. NA in release supernatants from hippocampal slices was found to be increased in response to stimulation with high K+ (30 mM), an effect which was dependent on Ca2+. Basal NA release was also Ca2+ dependent. Isolation-rearing did not significantly alter either basal or K+-stimulated release. Clonidine (10 microM) caused an inhibition of basal NA release in both regions and in both rearing groups, however there was no significant effect of isolation-rearing for this response although the response tended to be greater in the hippocampus from isolates. Idazoxan (10 microM) significantly increased basal NA release in hippocampal and hypothalamic slices in both rearing groups, but this effect was significantly greater in the hippocampus from isolation-reared rats. These findings suggest there may be a region-specific change in the sensitivity of the alpha2-adrenoceptor in isolates. Taken together with previous findings, there is evidence to suggest that isolation-rearing alters the sensitivity of the presynaptic terminal alpha2-autoreceptor in the hippocampus.