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Neuropeptide S differently modulates alcohol-related behaviors in alcohol-preferring and non-preferring rats

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Abstract

Rationale

Neuropeptide S (NPS) displays unique pharmacological properties and induces both anxiolytic and pro-stress/arousal activities. Previous studies performed using Wistar rats demonstrated that NPS facilitated alcohol and cocaine seeking but did not affect alcohol or cocaine consumption.

Objectives

Here, we investigated the effects of NPS in Marchigian Sardinian alcohol-preferring (msP) rats, a rat strain characterized by excessive alcohol consumption comorbid with heightened anxiety and depressive-like phenotypes. Specifically, we evaluated the effect of NPS on operant alcohol self-administration by msP rats compared to Wistar rats. The effect of NPS on cue-induced reinstatement of alcohol seeking in msP rats was also evaluated. Finally, using the open field test (OFT) and the elevated plus maze (EPM), we evaluated the effects of NPS on locomotor activity and anxiety.

Results

NPS reduced alcohol self-administration but did not affect cue-induced reinstatement in the msP rat. In addition, NPS induced reinstatement of extinguished alcohol seeking in Wistar rats without affecting alcohol intake. In the EPM task, NPS, in accordance with its anxiolytic activity, increased the time spent in the open arm of the arena by msP rats, although this effect was not observed in Wistar rats.

Conclusions

These data suggest that the effect of NPS is strongly influenced by the genetic background of the animal. In Wistar rats, NPS acts as a pro-arousal agent to promote the reinstatement of alcohol seeking. However, when alcohol drinking is motivated by or associated with a state of pathological anxiety, NPS attenuates alcohol consumption and seeking due to its anxiolytic activity.

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Acknowledgments

We thank Rina Righi and Mariangela Fiorelli for animal care and Alfredo Fiorelli for technical support. This work was supported by National Institutes of Health grants RO1 AA017447 and RO1 AA014351 from the National Institute on Alcohol Abuse and Alcoholism.

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Authors and Affiliations

  1. School of Pharmacy, Pharmacology Unit, University of Camerino, Building of Experimental Medicine, Via Madonna delle Carceri 9, Camerino, MC, 62032, Italy

    Nazzareno Cannella, Marsida Kallupi, Hong Wu Li, Serena Stopponi, Carlo Cifani, Roberto Ciccocioppo & Massimo Ubaldi

Authors
  1. Nazzareno Cannella
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  2. Marsida Kallupi
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  3. Hong Wu Li
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  4. Serena Stopponi
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  5. Carlo Cifani
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  6. Roberto Ciccocioppo
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  7. Massimo Ubaldi
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Corresponding author

Correspondence to Massimo Ubaldi.

Ethics declarations

All procedures adhered to the European Community Council Directive and the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and were approved by the Ethics Committee of the University of Camerino (Protocol no. 1/2012).

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Cannella, N., Kallupi, M., Li, H.W. et al. Neuropeptide S differently modulates alcohol-related behaviors in alcohol-preferring and non-preferring rats. Psychopharmacology 233, 2915–2924 (2016). https://doi.org/10.1007/s00213-016-4333-7

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  • DOI: https://doi.org/10.1007/s00213-016-4333-7

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