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Abstract
Increasing oxytocin (OT) in the central amygdala (CeA) via infusion of a selective OT agonist (Viviani et al., 2011) or optogenetic stimulation of hypothalamic neurons (Knobloch et al., 2012) reduced conditioned freezing responses. In contrast, intracerebroventricular (i.c.v.) administration of OT increased conditioned freezing responses (Toth, Neumann, & Slattery, 2012). The route of administration may account for these differences in fear responses. Specifically, i.c.v. OT may target other amygdala areas such as the basolateral amygdala (BLA), thereby increasing freezing responses. This thesis investigated CeA and BLA infusions of OT on the acquisition and extinction of context conditioned fear responses. In two experiments investigating the effects of OT on fear acquisition, rats were trained to fear a context under a drug infusion and their retention of fear assessed when drug-free. Intra-CeA and intra-BLA infusions of OT had no effect on freezing responses across the conditioning session. However, fear responses were reduced at test indicating that OT impaired the acquisition of context conditioned fear. In 8 experiments investigating the effects of OT on fear extinction, rats were trained to fear a context, their fear extinguished under a drug infusion or the drug was infused immediately after extinction and their retention of extinguished fear assessed when drug-free. Infusion of OT into the CeA impaired, whereas infusion into the BLA facilitated the extinction of fear responses. This was blocked by co-infusion of a selective OT antagonist (OTA; desGly-NH2-d(CH2)5[D-Tyr2,Thr4]OVT) suggesting OT receptor specificity. OT infused into the BLA after extinction training had no effect on fear responses at test suggesting that OT does not affect the consolidation of extinction learning in the BLA. In contrast, OT infused into the CeA after extinction training reduced fear responses at test suggesting that OT had impaired the consolidation of extinction learning in this nucleus. OTA infused into the CeA reduced freezing responses across the extinction session whereas BLA-OTA had no effect. This suggests that endogenous CeA-OT maintains freezing responses across the extinction session whereas endogenous BLA-OT may not influence fear responding or the depression of fear responses that occur across extinction training. Lastly, an infusion of muscimol into the BLA and CeA had effects similar to OT on long-term depression of fear responses suggesting that OT may influence fear extinction via an increase in GABA activity.