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Amphetamine-induced appetitive 50-kHz calls in rats: a marker of affect in mania?

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Abstract

Rationale

Animal models aimed to mimic mania have in common the lack of genuine affective parameters. Although rodent amphetamine-induced hyperlocomotion is a frequently used behavioral model of mania, locomotor activity is a rather unspecific target for developing new pharmacological therapies, and does not necessarily constitute a cardinal symptom in bipolar disorder (BD). Hence, alternative behavioral markers sensitive to stimulants are required.

Objectives

Since d-amphetamine induces appetitive 50-kHz ultrasonic vocalizations (USV) in rats, we asked whether established or potential antimanic drugs would inhibit this effect, thereby possibly complementing traditional analysis of locomotor activity.

Methods

Amphetamine-treated rats (2.5 mg/kg) were systemically administered with the antimanic drugs lithium (100 mg/kg) and tamoxifen (1 mg/kg). Since protein kinase C (PKC) activity has been implicated in the pathophysiology of bipolar disorder and the biochemical effects of mood stabilizers, the new PKC inhibitor myricitrin (10, 30 mg/kg) was also evaluated.

Results

We demonstrate for the first time that drugs with known or potential antimanic activity were effective in reversing amphetamine-induced appetitive 50-kHz calls. Treatments particularly normalized amphetamine-induced increases of frequency-modulated calls, a subtype presumably indicative of positive affect in the rat.

Conclusions

Our findings suggest that amphetamine-induced 50-kHz calls might constitute a marker for communicating affect that provides a useful model of exaggerated euphoric mood and pressured speech. The antimanic-like effects of the PKC inhibitors tamoxifen and myricitrin support the predictive and etiological validity of both drugs in this model and highlight the role of PKC signaling as a promising target to treat mania and psychosis-related disorders.

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Acknowledgements

This work was supported by the grant Schw 559/10-1 from the Deutsche Forschungsgemeinschaft. M. Pereira was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil). R. Andreatini received a researcher fellowship from CNPq. JC Brenes was funded by Deutscher Akademischer Austauschdienst (DAAD, Germany), and the University of Costa Rica.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81540-990, Brazil

    Marcela Pereira & Roberto Andreatini

  2. Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, 35032, Marburg, Germany

    Rainer K. W. Schwarting & Juan C. Brenes

  3. Institute for Psychological Research, University of Costa Rica, Rodrigo Facio Campus, 2060, San Pedro, Costa Rica

    Juan C. Brenes

  4. Neuroscience Research Center, University of Costa Rica, Rodrigo Facio Campus, 2060, San Pedro, Costa Rica

    Juan C. Brenes

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  1. Marcela Pereira
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  2. Roberto Andreatini
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  3. Rainer K. W. Schwarting
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  4. Juan C. Brenes
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Corresponding authors

Correspondence to Rainer K. W. Schwarting or Juan C. Brenes.

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Pereira, M., Andreatini, R., Schwarting, R.K.W. et al. Amphetamine-induced appetitive 50-kHz calls in rats: a marker of affect in mania?. Psychopharmacology 231, 2567–2577 (2014). https://doi.org/10.1007/s00213-013-3413-1

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  • DOI: https://doi.org/10.1007/s00213-013-3413-1

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