Differential brain-derived neurotrophic factor expression in limbic brain regions following social defeat or territorial aggression

Abstract

Syrian hamsters readily form dominant-subordinate relationships under laboratory conditions. Winning or losing in agonistic encounters can have striking, long-term effects on social behavior, but the mechanisms underlying this experience-induced behavioral plasticity are unclear. The present study tested the hypothesis that changes in brain-derived neurotrophic factor (BDNF) may at least in part mediate this plasticity. Male hamsters were paired for 15-min using a resident-intruder model, and individuals were identified as winners or losers on the basis of their behavior. BDNF was examined with in situ hybridization 2 hr after treatment during the consolidation period of emotional learning. Losing animals had significantly more BDNF mRNA in the basolateral (BLA) and medial (MeA) nuclei of the amygdala when compared with winning animals as well as novel cage and home cage controls. Interestingly, winning animals had significantly more BDNF mRNA in the dentate gyrus of the dorsal hippocampus than did losing animals, novel, and home cage controls. No conflict-related changes in BDNF mRNA were observed in several other regions including the bed nucleus of the stria terminalis and central amygdala. Next, we demonstrated that K252a, a Trk receptor antagonist, significantly reduced the acquisition of conditioned defeat when administered within the BLA. These data support a model in which BDNF-mediated plasticity within the BLA supports learning of submission or subordinate social status in losing animals, whereas BDNF-mediated plasticity within the hippocampus may instantiate aspects of winning such as control of a territory in dominant animals.

Figure 1

Mean (± standard error of the mean) of BDNF mRNA in the BLA, MeA, and DHPC DG in losers, winners, and novel and home cage controls. Unshared letters indicate a significant difference among groups (P < 0.004).

Figure 2

BDNF mRNA in the BLA, MeA, and DHPC DG 2hr after exposure to an agonistic encounter at low and high power magnification.

Figure 3

Histological reconstructions of injection sites of animals receiving infusions into the BLA in Experiment 2. Black dots represent the site of injection in one or more animals. Black triangles represent anatomical misses. Drawings are adapted from Morin and Wood (2001).

Figure 4

Acquisition of conditioned defeat. Total duration (mean ± S.E.M.) of submissive/defensive, aggressive, social, and nonsocial behavior displayed by defeated hamsters during a 5-min test with a non-aggressive intruder. Animals received bilateral infusions of vehicle or K252a into the BLA immediately before being defeated by a resident aggressor for 15 min on the previous day. Asterisk indicates a significant difference from vehicle (p < 0.05).