Our approach to the neurobiology of anxiety has become increasingly developmental with a focus on both genetic components (using inbred strains) and the contribution of early experience (using diverse rearing conditions). Inbred rat strains selected for emotional reactivity--the Maudsley reactive and non-reactive strains--showed no differences in brain benzodiazepine receptor binding, but could be distinguished by the number of adenosine receptors in the molecular layer of the cerebellum. Preliminary data suggest higher levels of norepinephrine in the frontal cortex and the locus coeruleus of the reactive strain. The importance of rearing condition was demonstrated in rhesus monkeys raised with or without control over appetitive (non-aversive) stimuli. This """"""""mastery-yoked"""""""" paradigm was employed throughout the first year of life for animals raised in peer groups. Two years later the """"""""mastery"""""""" animals--i.e. those raised with control over toys and food treats--showed less distress when isolated in comparison to individuals reared in the """"""""yoked"""""""" condition--who received identical toys and treats on a non-contingent basis. Following administration of the benzodiazepine receptor inverse agonist Beta-CCE, mastery animals appeared hostile whereas yoked animals appeared fearful and withdrawn. Using in vitro receptor autoradiography, brain receptors for both corticotropin releasing factor (CRF) and benzodiazepines were first found at 17 days gestation in the rat (i.e. 4 days prior to birth). As other peptide hormones when administered early in life can have long-term consequences on behavior and neural receptor sensitivity, we investigated the results of CRF administration during the first week of life. Rat pups given CRF daily from day 1-7 were not consistently more emotionally reactive behaviorally, but showed increased corticosterone levels following isolation in adulthood.
