Abstract
The hippocampus is part of a neural network which regulates the renewal of fear following extinction. Both the ventral (VH) and dorsal (DH) hippocampus have been shown to be necessary for renewal, however the critical receptors and neurotransmitters mediating these contributions are poorly understood. One candidate mechanism is the kappa opioid receptor (KOR) system, which has been implicated in fear learning and anxiety. Here we examined the effect of the KOR antagonist norbinaltorphamine hydrochloride (norBNI), infused into either the VH or DH, on the renewal of extinguished fear. We found that an infusion of norBNI into the VH significantly reduced the relapse of fear on test compared to that seen in saline controls (Experiment 1), while similar infusions of norBNI into the DH had no effect on renewal (Experiment 2). These findings show that hippocampal KORs are involved in fear renewal and also identify a dissociation in the contribution of VH and DH KORs to the expression of renewed fear.
Highlights
Animals will readily learn to fear a neutral cue such as a tone, following pairings of that cue with an aversive outcome like footshock
Because kappa opioid receptor (KOR) are expressed in moderately high levels in the hippocampus [16], here we studied a potential role for hippocampal KORs in the renewal of extinguished fear
We found a dissociation in the contribution of hippocampal KORs, such that KORs in the ventral hippocampus (VH), but not the dorsal hippocampus (DH), mediate the renewal of fear
Summary
Animals will readily learn to fear a neutral cue such as a tone, following pairings of that cue with an aversive outcome like footshock. Herry and colleagues [9] showed that BA neurons active during renewal receive projections from VH, and disconnecting VH from either the mPFC or BA [10], or lesioning VH [11], disrupts renewal This basic circuitry of fear renewal has begun to be elucidated, the mechanisms through which this circuit functions remain poorly understood. There has been increasing interest in the potential therapeutic merit of the kappa opioid receptor (KOR) system in a range of psychiatric pathologies, including anxiety and depression This is due in part to studies demonstrating the anxiolytic and antidepressant-like properties of KOR antagonists like norBNI [12,13]. We found a dissociation in the contribution of hippocampal KORs, such that KORs in the VH, but not the DH, mediate the renewal of fear
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