Abstract
Rationale
Fifty-kilohertz ultrasonic vocalizations (USV) in rats are believed to express inter-individual differences in trait-like positive affective phenotypes. Emission of 50-kHz USV can be induced by amphetamine (AMPH) to model mania-like positive affect, raising the possibility that predispositions for high 50-kHz USV production confer susceptibility to mania-like states. Such 50-kHz USV presumably express the sender’s motivation for social contact and elicit social approach behavior in receivers.
Objectives
We recently showed that AMPH-induced 50-kHz USV are paralleled by mania-like patterns of enhanced social approach behavior towards playback of 50-kHz USV. Here, we assessed whether these AMPH effects are dependent on trait-like inter-individual differences in 50-kHz USV production.
Methods
To this aim, we subdivided juvenile rats into those emitting low (LC) and high (HC) rates of baseline 50-kHz USV and compared them across four AMPH dosage conditions: 0.0, 0.5, 1.0, and 2.5 mg/kg.
Results
HC rats were considerably more susceptible to AMPH in inducing 50-kHz USV than LC rats, consistently across all examined doses. They further appeared to attribute more incentive salience to signals of rewarding social contact, as evidenced by enhanced social approach behavior towards 50-kHz USV playback, a response pattern also seen in LC rats after receiving AMPH treatment. HC but not LC rats emitted aversive 22-kHz USV following 50-kHz USV playback, indicating increased proneness to experience negative affective states if no actual social consequence followed the incentive signal.
Conclusion
Inter-individual differences in 50-kHz USV map onto a unique trait-like socio-affective phenotype associated with enhanced emotional reactivity towards social and non-social reward, possibly conferring risk to mania-like states.
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Funding
This work was supported by grants from the Deutsche Forschungsgemeinschaft to R.S. (DFG SCHW 559/14-1) and to M.W. (DFG WO 1732/4-1).
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All experimental procedures were in accordance with the current European guidelines and approved by the ethics committee of the local government (Regierungspräsidium Gießen; MR20/35 Nr.1/2015).
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The authors declare that they have no competing interests.
Electronic supplementary material
Supplementary Figure 1
Inter-individual differences in spontaneous 50-kHz USV emission correlate with amphetamine-induced 50-kHz USV but less robust with amphetamine-induced psychomotor hyperactivity. Scatterplots depicting the correlation between the number of baseline 50-kHz USV in the open field on day 1 and (I) the number of 50-kHz USV on day 3 (A-D), (II) distance traveled on day 1 (A`-D`), and (III) distance traveled on day 3 (A``-D``) in rats treated with vehicle or amphetamine (AMPH; 0.0 mg/kg-2.5 mg/kg, i.p.) on day 3. In vehicle controls, the number of 50-kHz USV on day 1 was highly positively correlated with 50-kHz USV production on day 3, indicating that baseline 50-kHz USV emission is stable over time (A). Such high correlations were also seen in rats treated with AMPH on day 3, showing that baseline 50-kHz USV emission predicts AMPH-induced 50-kHz USV (B-D). By contrast, no stable and consistent relationships were seen between baseline 50-kHz USV on day 1 and locomotor activity on day 1 (A`-D`) or AMPH-induced psychomotor hyperactivity on day 3 (A``-D``), except in vehicle controls, where 50-kHz USV emission was positively correlated with distance traveled on day 1 (A`), but not day 3 (A``), and in rats treated with 0.5 mg/kg AMPH, where 50-kHz USV correlated both with distance traveled on day 1 (B`) and day 3 (B``). *p < 0.05 (Spearman’s rho). N = 16 per group. (JPEG 228 kb)
Supplementary Figure 2
Baseline and amphetamine-induced acoustic call parameters are similar in rats emitting high compared to low spontaneous 50-kHz USV. Bar graphs depicting call duration (A-D), peak amplitude (A`-D`), peak frequency (A``-D``), and frequency modulation (A```-D```) of 50-kHz USV in rats emitting low (LC; white) and high (HC; black) rates of 50-kHz USV treated with vehicle or amphetamine (AMPH; 0.0 mg/kg-2.5 mg/kg, i.p.). Acoustic call parameters were highly comparable between LC and HC across all experimental groups. In vehicle controls, only call duration was higher in HC compared to LC (A), while in rats treated with 2.5 mg/kg AMPH, peak frequency was minimally reduced in HC compared to LC (D``). No other comparisons were significantly different. Data are presented as mean ± SEM. *p < 0.05 (Mann-Whitney-U test). N = 4-8 per group. (JPEG 188 kb)
Supplementary Figure 3
Inter-individual differences in spontaneous 50-kHz USV emission predict social approach behavior towards playback of 50-kHz USV under drug-free but not amphetamine conditions. Scatterplots depicting the correlation between the number of baseline 50-kHz USV in the open field on day 1 and the preference for proximal vs. distal arms during 50-kHz USV playback in the radial maze playback paradigm. The preference score was calculated as follows: (proximal – distal) / (proximal + distal), using either arm entries (A-D) or time spent on arms (A`-D`) during the 1min playback presentation of 50-kHz USV, with +1 reflecting 100% preference for proximal arms and -1 reflecting 100% preference for distal arms. Only in vehicle controls, the number of baseline 50-kHz USV on day 1 was positively correlated with the preference for proximal arms during 50-kHz USV playback. The correlation was significant for the preference score based on the numbers of arm entries (A), while there was a trend for a significant relationship for the preference score based on the time spent on arms (p = 0.059; A`). By contrast, no significant correlation was seen between baseline 50-kHz USV on day 1 and social approach behavior in all AMPH-treated groups (B-D; B`-D`). (*)p < 0.10; *p < 0.05 (Spearman’s rho). N = 15-16 per group. (JPEG 152 kb)
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Engelhardt, K.A., Schwarting, R.K.W. & Wöhr, M. Mapping trait-like socio-affective phenotypes in rats through 50-kHz ultrasonic vocalizations. Psychopharmacology 235, 83–98 (2018). https://doi.org/10.1007/s00213-017-4746-y
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DOI: https://doi.org/10.1007/s00213-017-4746-y