Abstract
Safety signals (SSs) have been shown to reinforce instrumental avoidance behavior due to their ability to signal the absence of an aversive event; however, little is known of their neural mediation. This study investigated whether infusions of d-amphetamine in the nucleus accumbens (Nac), previously shown to potentiate responding for appetitive conditioned reinforcers (CRfs), also regulate avoidance responding for a SS. Rats were trained on a free-operant task in which lever-press responses avoided shock and were reinforced with an auditory SS. Rats were then cannulated in the Nac core (NacC) or shell (NacS) and infused with d-amphetamine and, in separate NacS groups, other drugs, before extinction sessions with the SS present or absent following responding. Selective effects of d-amphetamine were found in the NacS, but not in the NacC, when the SS was present in the session. A significant increase in response rate during the presentation of the SS reflected a disruption of its fear-inhibiting properties. In parallel, a decrease in avoidance response rate reflected the reduced influence of the SS as a CRf. Inactivation of the NacS reduced avoidance responding only when the SS was present in the session, whereas the D1–D2 DA receptor antagonist α-flupenthixol reduced responding both before and during the SS regardless of the presence of the SS. Atomoxetine (ATO), a selective noradrenaline reuptake inhibitor, had no effect on responding. These results indicate a role for the NacS in the mediation of the conditioned reinforcing properties of a SS. These effects appear to be modulated by dopaminergic mechanisms but seem distinct from those previously reported with food-related CRfs.
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Acknowledgements
This study was supported by a joint Wellcome Trust Programme grant to TWR, JW Dalley, BJ Everitt, AC Roberts, and BJ Sahakian (089589/z/09/z). ABPF was supported by an MRC Case studentship and GPU was supported by a Marie Curie Fellowship. We also thank Dr Rudolf Cardinal for his helpful comments and critiques of the manuscript. The study was completed within the Behavioural and Clinical Neuroscience Institute, supported by a joint award from the MRC and the Wellcome Trust.
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Fernando, A., Urcelay, G., Mar, A. et al. The Role of the Nucleus Accumbens Shell in the Mediation of the Reinforcing Properties of a Safety Signal in Free-Operant Avoidance: Dopamine-Dependent Inhibitory Effects of d-amphetamine. Neuropsychopharmacol 39, 1420–1430 (2014). https://doi.org/10.1038/npp.2013.337
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DOI: https://doi.org/10.1038/npp.2013.337
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