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Critical involvement of 5-HT2C receptor function in amphetamine-induced 50-kHz ultrasonic vocalizations in rats

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Abstract

Rationale

Rats emit various distinct types of ultrasonic vocalizations (USV), with high-frequency 50-kHz USV typically occurring in appetitive situations being elicited by administering drugs of abuse, most notably amphetamine (AMPH), possibly reflecting drug wanting/craving and/or liking.

Objectives

Because 50-kHz USV emission is, at least in part, dopamine (DA) dependent and 5-HT2C agonists inhibit DA neurotransmission, we hypothesized that AMPH-induced 50-kHz USV can be attenuated by pretreatment with a 5-HT2C agonist.

Methods

In experiments I and II, a dose-response curve for AMPH-induced 50-kHz USV was established, and the partial dependency of AMPH-induced 50-kHz USV on DA neurotransmission was validated by pretreatment with the D2-antagonist eticlopride. In experiment III, rats were pretreated with the 5-HT2C agonist CP 809,101 (0.0, 0.3, 1.0, 3.0, and 10 mg/kg), while in experiment IV, CP 809,101 (3.0 mg/kg), the 5-HT2C antagonist SB 242084 (1.0 mg/kg), or the combination of the two, was applied before AMPH administration (2.0 mg/kg). Finally, in experiment V, rats were treated with SB 242084 (0.0, 0.1, 0.3, and 1.0 mg/kg) only, i.e., in absence of AMPH.

Results

The 5-HT2C agonist CP 809,101 dose-dependently blocked AMPH-induced 50-kHz USV, most notably trills, a call subtype that is considered to exclusively reflect a positive affective state, while the 5-HT2C antagonist SB 242084 induced opposite effects. Moreover, SB 242084 induced 50-kHz USV by its own.

Conclusions

5-HT2C receptors are critically involved in AMPH-induced 50-kHz USV, with 5-HT2C antagonism resulting in a stimulant-like effect. Attenuation of drug wanting/craving and/or liking by coadministration of a 5-HT2C agonist could be a translational pharmacodynamic biomarker.

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Acknowledgments

This work was supported by a grant by the Deutsche Forschungsgemeinschaft to M.W. (DFG WO 1732/1-1). The authors wish to thank Gisela Kreuzenberger for excellent technical assistance.

Conflict of interests

M.M.v.G. is full employee of AbbVie Deutschland GmbH & Co. KG and shareholder of AbbVie and Abbott. M.W. is scientific advisor of Avisoft Bioacoustics.

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  1. Marcel M. van Gaalen

    Present address: Encepharm, Hans-Adolf-Krebs-Weg 9, 37077, Göttingen, Germany

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

    Markus Wöhr, Henrike Rippberger & Rainer K. W. Schwarting

  2. AbbVie Deutschland GmbH & Co. KG, Neuroscience Research, Knollstr. 1, 67061, Ludwigshafen, Germany

    Marcel M. van Gaalen

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Wöhr, M., Rippberger, H., Schwarting, R.K.W. et al. Critical involvement of 5-HT2C receptor function in amphetamine-induced 50-kHz ultrasonic vocalizations in rats. Psychopharmacology 232, 1817–1829 (2015). https://doi.org/10.1007/s00213-014-3814-9

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