Olfactory association learning and brain-derived neurotrophic factor in an animal model of early deprivation.

Animal models can serve to explore neural mechanisms underlying the effects of stressful early experiences on behaviors supporting attachment. Neonatal rats primarily use olfaction for attachment, and Brain-Derived Neurotrophic Factor (BDNF) may be a key transcription target in olfactory association learning. In this experiment, neonatal male and female rats were isolated individually for 3 hr daily in the first week of life while their dams were left with partial litters (Early Deprivation, ED) or remained undisturbed (Control). At 1 week of age, subjects were tested using a 2-day classical conditioning paradigm. The conditioned group (O/M) was exposed to a novel odor paired with a milk infusion. Three additional groups included an unpaired odor and milk exposure group (O/M unP), an odor exposure alone group (O/NM), and neither an odor nor a milk group (NO/NM). Learning the odor association, as revealed in a position preference for the novel odor, was accompanied by an increase in hippocampal BDNF in O/M subjects from undisturbed Control litters. BDNF levels were also positively related to degree of preference for the odor in the O/M Control group. ED subjects did not make the classically conditioned odor association and did not show an increase in hippocampal BDNF. ED increased BDNF levels in the olfactory bulb compared to Controls regardless of training group; individual levels were not correlated with performance because samples were pooled. These results suggest that changes in the transcription of BDNF may underlie some of the long-term consequences of the early stress of maternal separation.