Transitions in infant learning are modulated by dopamine in the amygdala

Abstract

Behavioral transitions characterize development. Young infant rats paradoxically prefer odors that are paired with shock, but older pups learn aversions. This transition is amygdala and corticosterone dependent. Using microarrays and microdialysis, we found downregulated dopaminergic presynaptic function in the amygdala with preference learning. Corticosterone-injected 8-d-old pups and untreated 12-d-old pups learned aversions and had dopaminergic upregulation in the amygdala. Dopamine injection into the amygdala changed preferences to aversions, whereas dopamine antagonism reinstated preference learning.

Figure 1

Role of shock on corticosterone and behavior. (a) Pups at 8 days of age are within the stress hypo-responsive period when mild shock (0.5 mA) does not elevate mean plasma corticosterone levels. In contrast, injection of corticosterone in a saline vehicle (at 24 hours and 30 minutes before conditioning; 3.0 mg kg^–1, i.p.) produces elevated plasma corticosterone levels following shock, equal about to that induced by mild shock at 12 days of age. (ANOVA: significant group effect; F_{3, 9} = 9.95, P < 0.005). (b) Infant odor-shock conditioning paradoxically causes an odor preference in 8–day–old pups, although similar conditioning in 12–day–old pups causes an odor aversion. This odor aversion can be learned in 8–day–old animals if injected with corticosterone prior to conditioning. Control groups (unpaired odor-shock and odor-only pups) failed to learn either an aversion or preference, regardless of the age or corticosterone treatment. The dotted line represents chance performance. [ANOVA: significant interaction between conditioning groups and drug treatment (F_4,49 = 16.07, P < 0.0001)]. For all figures: bars represent means ± s.e.m.; blue indicates conditions under which preferences are learned and red indicates conditions under which aversions are learned.

Figure 2

Dopamine efflux and manipulation. (a) Measurements of extracellular dopamine efflux within the amygdala at PN–8 before (baseline), during (conditioning) and after (recovery) conditioning. Paired odor-shock treatment, which normally produces an odor preference, decreased amygdala dopamine, whereas in PN–8 animals that normally learn an aversion after injection with corticosterone showed increased amygdala dopamine [Data collapsed over 45 minute bins for presentation. significant interaction between conditioning groups × time; F_18,135 = 88.81, P < 0.0001]; (b). PN–8 pups learning an aversion (with corticosterone) had increased amygdala levels of dopamine [significant interaction between conditioning groups × time; F_18,135 = 71.87, P < 0.0001]. Post-hoc Fisher tests revealed that all Paired groups were significantly different from the control groups (P < 0.001); (c) At 8 days of age, dopamine infused (3–6 μg 2 μl^–1; 0.1 μl min^–1 beginning 5 minutes prior to conditioning) into the amygdala resulted in a learned odor aversion during an odor-shock conditioning. Saline infused animals of the same age learned the expected preference for the odor [condition × infusion interaction; F_1,17 = 37.36, P < 0.0001]; (d) Blocking amygdala dopamine receptors with the receptor antagonist cis-Flupenthixol (20 μg 2 μl^–1 as per dopamine) caused PN–8 pups receiving corticosterone to switch to an odor preference rather than the odor aversion seen with corticosterone injection during an odor-shock conditioning in the same aged rats [interaction between conditioning groups, drugs infusion and corticosterone/saline; F_1,32 = 17.79, P < 0.0005].