Skip to main content
Log in

Activation of adenosine A2A receptors suppresses the emission of pro-social and drug-stimulated 50-kHz ultrasonic vocalizations in rats: possible relevance to reward and motivation

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Rats emit 50-kHz ultrasonic vocalizations (USVs) in response to pleasurable stimuli, and these USVs are considered a tool for investigating reward and motivation.

Objectives

This study aimed to clarify how activity of adenosine A2A receptors, which modulate reward and motivation, influences 50-kHz USV emission in rats.

Methods

Rats received one of the following treatments in a test cage: (1) acute administration of the A2A receptor agonist CGS 21680 (0.05–0.2 mg/kg, i.p.) during social interactions; (2) long-term amphetamine (1 or 2 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.) administration on alternate days, alone or with CGS 21680, followed after 7 days of discontinuation by test cage re-exposure, to assess drug-conditioning effects, and thereafter drug challenge; (3) acute administration of the D1/D2 receptor agonist apomorphine (4 mg/kg, i.p.), alone or with CGS 21680; and (4) long-term administration of the non-selective A1/A2A receptor antagonist caffeine (15 mg/kg, i.p.), on alternate days. USVs and locomotor activity were evaluated throughout the treatments.

Results

CGS 21680 attenuated 50-kHz USV emission stimulated by social interactions, amphetamine, apomorphine, and morphine, and rats administered CGS 21680 with amphetamine or morphine emitted fewer conditioned 50-kHz USVs upon test cage re-exposure, compared with rats administered amphetamine or morphine alone. Moreover, CGS 21680 administration prevented long-term changes in locomotor activity in amphetamine- and morphine-treated rats. Finally, caffeine had no effect on 50-kHz USVs.

Conclusions

These results indicate that activation of A2A receptors attenuates 50-kHz USV emission in rats and further elucidate how these receptors modulate the motivational properties of natural and pharmacological stimuli.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

Download references

Acknowledgments

The authors are grateful to Ms. Flora Corrias and Mr. Riccardo Orrù for their help with the recordings of vocalizations and locomotor activity.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nicola Simola.

Ethics declarations

All experiments were conducted in accordance with the guidelines for animal experimentation of the EU directives (2010/63/EU; L.276; 22 September 2010) and with the guidelines approved by the Ethical Committee of the University of Cagliari.

Funding

This work was supported by funds from Fondazione Banco di Sardegna (project number 2014.0395) and by funds from the Regione Autonoma della Sardegna (Legge Regionale 7 Agosto 2007, N.7, annualità 2010). Dr. Nicola Simola gratefully acknowledges the Sardinian Regional Government for financial support (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007–2013—Axis IV Human Resources, Objective l.3, Line of Activity l.3.1 “Avviso di chiamata per il finanziamento di Assegni di Ricerca”).

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table 1

Summary of the results of ANOVA followed by Tukey’s post hoc test obtained in day 1 of repeated treatment from rats administered amphetamine (1 or 2 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.). Each drug was administered alone or with the A2A receptor agonist CGS 21680 (0.05–0.2 mg/kg, i.p., 15 min before). Differences between the experimental groups are presented by comparing the group in each line with the group in each corresponding column. A = amphetamine, M = morphine, C = CGS 21680. ↑ = significantly higher compared with the group in the corresponding column; ↓ = significantly lower compared with the group in the corresponding column; n.s. = no significant difference compared with the group in the corresponding column; barred cells indicate that no statistical comparison between the two groups was performed. (DOC 89 kb)

Supplementary Table 2

Summary of the results of ANOVA followed by Tukey’s post hoc test obtained in day 5 of repeated treatment from rats administered amphetamine (1 or 2 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.). Each drug was administered alone or with the A2A receptor agonist CGS 21680 (0.05–0.2 mg/kg, i.p., 15 min before). Differences between the experimental groups are presented by comparing the group in each line with the group in each corresponding column. A = amphetamine, M = morphine, C = CGS 21680. ↑ = significantly higher compared with the group in the corresponding column; ↓ = significantly lower compared with the group in the corresponding column; n.s. = no significant difference compared with the group in the corresponding column; barred cells indicate that no statistical comparison between the two groups was performed. (DOC 91 kb)

Supplementary Table 3

Summary of the results of ANOVA followed by Tukey’s post hoc test obtained in day 9 of repeated treatment from rats administered amphetamine (1 or 2 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.). Each drug was administered alone or with the A2A receptor agonist CGS 21680 (0.05–0.2 mg/kg, i.p.). Differences between the experimental groups are presented by comparing the group in each line with the group in each corresponding column. A = amphetamine, M = morphine, C = CGS 21680. ↑ = significantly higher compared with the group in the corresponding column; ↓ = significantly lower compared with the group in the corresponding column; n.s. = no significant difference compared with the group in the corresponding column; barred cells indicate that no statistical comparison between the two groups was performed. (DOC 91 kb)

Supplementary Table 4

Summary of the results of ANOVA followed by Tukey’s post hoc test obtained after drug challenge (day 16) with amphetamine (1 or 2 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.) in rats repeatedly treated with either drug. Each drug was administered alone or with the A2A receptor agonist CGS 21680 (0.05–0.2 mg/kg, i.p.) during repeated treatment (days 1–9), whereas no CGS 21680 was administered in day 16. Differences between the experimental groups are presented by comparing the group in each line with the group in each corresponding column. A = amphetamine, M = morphine, C = CGS 21680. ↑ = significantly higher compared with the group in the corresponding column; ↓ = significantly lower compared with the group in the corresponding column; n.s. = no significant difference compared with the group in the corresponding column; barred cells indicate that no statistical comparison between the two groups was performed. (DOC 257 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Simola, N., Costa, G. & Morelli, M. Activation of adenosine A2A receptors suppresses the emission of pro-social and drug-stimulated 50-kHz ultrasonic vocalizations in rats: possible relevance to reward and motivation. Psychopharmacology 233, 507–519 (2016). https://doi.org/10.1007/s00213-015-4130-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-015-4130-8

Keywords

Navigation