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Stimulus-specific and differential distribution of activated extracellular signal-regulated kinase in the nucleus accumbens core and shell during Pavlovian-instrumental transfer

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Abstract

The ability of reward-predictive cues to potentiate reward-seeking behavior—a phenomenon termed Pavlovian-instrumental transfer (PIT)—depends on the activation of extracellular signal-regulated kinase (ERK) in the nucleus accumbens (NAc). Here, we utilized immunohistochemistry to investigate the subregional pattern of ERK activation during PIT, and the contribution of different elements in the PIT condition to the distribution of ERK signaling in the NAc of rats. We found that the occurrence of reward-seeking behavior (lever pressing) did not affect ERK activation in either the core or the shell of the NAc. In contrast, presentation of the reward-predictive cue (auditory conditioned stimulus) caused a significant increase in ERK activation in both subregions of the NAc, with the effect being slightly more robust in the core than the shell. Different from the pattern evoked by the reward-predictive cue, presentation of the reward itself (food pellets) had no effect on ERK activation in the core but caused a pronounced increase in ERK activation in the shell. Taken together, our results demonstrate that ERK signaling in the NAc during PIT involves both the core and the shell and is driven by the conditioned cue irrespective of whether the situation permits engagement in reward-seeking behavior. Furthermore, our results show that the subregional distribution of ERK signaling in the NAc evoked by rewards differs from that evoked by cues that predict them. The stimulus-specific differential pattern of ERK signaling described here may present the molecular complement to stimulus-specific increases in NAc cell firing reported previously.

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Acknowledgments

The work described here was supported by NSF training grant DGE-9987588, the National Institutes of Health grants DA027679, NDS046423 and NCRR-UL1RR024153, and a grant from the Office of the Senior Vice Chancellor, Health Sciences, University of Pittsburgh. We thank Catherine-Anne Domjan-Yuhas, Michael Light, Jocelyn Mauna, and Jim Remus for their technical assistance, and Dr. Susan Sesack for guidance with the immunohistochemical analyses and comments on the manuscript.

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  1. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, 15213, USA

    Merissa L. Remus

  2. Department of Neurobiology, University of Pittsburgh School of Medicine, 6064 Biomedical Science Tower 3, 3501 Fifth Ave, Pittsburgh, PA, 15260, USA

    Edda Thiels

  3. Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Edda Thiels

  4. Center for the Neural Basis of Cognition, Carnegie Mellon University and the University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Merissa L. Remus & Edda Thiels

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  1. Merissa L. Remus
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Correspondence to Edda Thiels.

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Remus, M.L., Thiels, E. Stimulus-specific and differential distribution of activated extracellular signal-regulated kinase in the nucleus accumbens core and shell during Pavlovian-instrumental transfer. Brain Struct Funct 218, 913–927 (2013). https://doi.org/10.1007/s00429-012-0438-x

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