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Reward-potentiating effects of D-1 dopamine receptor agonist and AMPAR GluR1 antagonist in nucleus accumbens shell and their modulation by food restriction

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Abstract

Rationale

Previous studies have suggested that chronic food restriction (FR) increases sensitivity of a neural substrate for drug reward. The neuroanatomical site(s) of key neuroadaptations may include nucleus accumbens (NAc) where changes in D-1 dopamine (DA) receptor-mediated cell signaling and gene expression have been documented.

Objectives

The purpose of the present study was to begin bridging the behavioral and tissue studies by microinjecting drugs directly into NAc medial shell and assessing behavioral effects in free-feeding and FR subjects.

Materials and methods

Rats were implanted with microinjection cannulae in NAc medial shell and a subset were implanted with a stimulating electrode in lateral hypothalamus. Reward-potentiating effects of the D-1 DA receptor agonist, SKF-82958, AMPAR antagonist, DNXQ, and polyamine GluR1 antagonist, 1-na spermine, were assessed using the curve-shift method of self-stimulation testing. Motor-activating effects of SKF-82958 were also assessed.

Results

SKF-82958 (2.0 and 5.0 μg) produced greater reward-potentiating and motor-activating effects in FR than ad libitum fed (AL) rats. DNQX (1.0 μg) and 1-na spermine (1.0 and 2.5 μg) selectively decreased the x-axis intercept of rate–frequency curves in FR subjects, reflecting increased responding for previously subthreshold stimulation.

Conclusions

Results suggest that FR may facilitate reward-directed behavior via multiple neuroadaptations in NAc medial shell including upregulation of D-1 DA receptor function involved in the selection and expression of goal-directed behavior, and increased GluR1-mediated activation of cells that inhibit nonreinforced responses.

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Authors and Affiliations

  1. Department of Psychiatry, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA

    Kenneth D. Carr, Soledad Cabeza de Vaca, Yanjie Sun & Lily S. Chau

  2. Department of Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA

    Kenneth D. Carr

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  1. Kenneth D. Carr
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  2. Soledad Cabeza de Vaca
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  3. Yanjie Sun
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  4. Lily S. Chau
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Correspondence to Kenneth D. Carr.

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This research was supported by DA03956 from NIDA/NIH.

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Carr, K.D., Cabeza de Vaca, S., Sun, Y. et al. Reward-potentiating effects of D-1 dopamine receptor agonist and AMPAR GluR1 antagonist in nucleus accumbens shell and their modulation by food restriction. Psychopharmacology 202, 731–743 (2009). https://doi.org/10.1007/s00213-008-1355-9

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  • DOI: https://doi.org/10.1007/s00213-008-1355-9

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