title: 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.
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.
authors: 1] Department of Psychology, University of Cambridge, Cambridge, UK [2] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge,UK.
authors: Anushka B P
authors: AB
authors: Fernando
authors: 1] Department of Psychology, University of Cambridge, Cambridge, UK [2] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge,UK.
authors: Gonzalo P
authors: GP
authors: Urcelay
authors: 1] Department of Psychology, University of Cambridge, Cambridge, UK [2] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge,UK.
authors: Adam C
authors: AC
authors: Mar
authors: 1] Department of Psychology, University of Cambridge, Cambridge, UK [2] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge,UK.
authors: Tony A
authors: TA
authors: Dickinson
authors: 1] Department of Psychology, University of Cambridge, Cambridge, UK [2] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge,UK.
authors: Trevor W
authors: TW
authors: Robbins
mesh_terms: D000161:Acoustic Stimulation; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004597:Electroshock; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005475:Flupenthixol / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D012054:Reinforcement, Psychology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D005475:Flupenthixol; D003913:Dextroamphetamine; D004298:Dopamine