Appetitive and aversive interactions during Pavlovian fear conditioning.

Abstract

The present thesis examined the behavioural and brain mechanisms of appetitive – aversive interactions in rats during Pavlovian fear conditioning. The first series of experiments (Chapter 3), characterised appetitive to aversive counterconditioning using a between-subjects design. An auditory conditioned stimulus (CS) was trained with a food unconditioned stimulus (US), after which the reward was omitted and the CS was reinforced with a footshock US. Prior appetitive training retarded the rate at which fear was acquired, compared to novel fear conditioning. Furthermore this retardation was not dependent on the presentation of the CS or US alone. Assessments of associative learning during appetitive- aversive interactions were made using appetitive to aversive superconditioning. Whereby a visual CS was trained with reward during Stage I then presented in compound with an auditory CS and reinforced with footshock during Stage II. Enhanced levels of fear were elicited by the auditory CS on test compared to a stimulus that was not presented in compound with the visual cue during Stage II. Furthermore retardation of fear was not alleviated by manipulations designed to restore the associability of the appetitive CS before fear conditioning but was alleviated by manipulations designed to increase the aversive quality of the footshock US. These findings are consistent with opponent interactions between the appetitive and aversive motivational systems and provide a behavioural approach for assessing the neural correlates of these appetitive-aversive interactions. The second series of experiments (Chapter 4) then examined potential neuroanatomical loci for appetitive-aversive interactions investigated in Chapter 3. Using phosphorylated mitogen activated protein kinase (pMAPK) several substrates indicated increased activity after counterconditioning consistent with enhanced prediction error, in the lateral amygdala, rostral agranular insular cortex (RAIC), nucleus accumbens and parts of the thalamus, whilst there was decreased activity in the ventrolateral quadrant of the periaqueductal gray (vlPAG). Intra-RAIC infusion of the MAPK kinase antagonist PD98059 during aversive conditioning reduced Stage II fear learning, whilst intra-vlPAG infusion of the μ-opioid receptor antagonist CTAP reduced magazine responses. These results suggest that appetitive to aversive counterconditioning is linked to heightened activity in the fear prediction error circuit.