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Psychopharmacology

, Volume 235, Issue 1, pp 83–98 | Cite as

Mapping trait-like socio-affective phenotypes in rats through 50-kHz ultrasonic vocalizations

  • K. -Alexander Engelhardt
  • Rainer K. W. Schwarting
  • Markus Wöhr
Original Investigation

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.

Keywords

Ultrasonic vocalization Social behavior Social approach Communication Individuality Amphetamine Dopamine Mania 

Notes

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).

Compliance with ethical standards

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).

Competing interests

The authors declare that they have no competing interests.

Supplementary material

213_2017_4746_Fig6_ESM.jpg (229 kb)
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)

213_2017_4746_Fig7_ESM.jpg (189 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)

213_2017_4746_Fig8_ESM.jpg (152 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)

References

  1. Ahrens AM, Nobile CW, Page LE, Maier EY, Duvauchelle CL, Schallert T (2013) Individual differences in the conditioned and unconditioned rat 50-kHz ultrasonic vocalizations elicited by repeated amphetamine exposure. Psychopharmacology 229:687–700CrossRefPubMedPubMedCentralGoogle Scholar
  2. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing, Arlington, VACrossRefGoogle Scholar
  3. Bauer CT, Banks ML, Blough BE, Negus SS (2013) Rate-dependent effects of monoamine releasers on intracranial self-stimulation in rats: implications for abuse liability assessment. Behav Pharmacol 24:448–458CrossRefPubMedPubMedCentralGoogle Scholar
  4. Blanchard RJ, Blanchard DC, Agullana R, Weiss SM (1991) Twenty-two kHz alarm cries to presentation of a predator, by laboratory rats living in visible burrow systems. Physiol Behav 50:967–972CrossRefPubMedGoogle Scholar
  5. Brenes JC, Lackinger M, Höglinger GU, Schratt G, Schwarting RK, Wöhr M (2016) Differential effects of social and physical environmental enrichment on brain plasticity, cognition, and ultrasonic communication in rats. J Comp Neurol 524:1586–1607CrossRefPubMedGoogle Scholar
  6. Brudzynski SM, Pniak A (2002) Social contacts and production of 50-kHz short ultrasonic calls in adult rats. J Comp Psychol 116:73-82CrossRefPubMedGoogle Scholar
  7. Brudzynski SM (2013) Ethotransmission: communication of emotional states through ultrasonic vocalization in rats. Curr Opin Neurobiol 23:310–317CrossRefPubMedGoogle Scholar
  8. Brudzynski SM, Komadoski M, St. Pierre J (2012) Quinpirole-induced 50 kHz ultrasonic vocalization in the rat: role of D2 and D3 dopamine receptors. Behav Brain Res 226:511–518CrossRefPubMedGoogle Scholar
  9. Brudzynski SM, Gibson B, Silkstone M, Burgdorf J, Kroes RA, Moskal JR, Panksepp J (2011a) Motor and locomotor responses to systemic amphetamine in three lines of selectively bred Long-Evans rats. Pharmacol Biochem Behav 100:119–124CrossRefPubMedGoogle Scholar
  10. Brudzynski SM, Silkstone M, Komadoski M, Scullion K, Druffus S, Burgdorf J, Kroes RA, Moskal JR, Panksepp J (2011b) Effects of intraaccumbens amphetamine on production of 50 kHz vocalizations in three lines of selectively bred Long-Evans rats. Behav Brain Res 217:32–40CrossRefPubMedGoogle Scholar
  11. Burgdorf J, Knutson B, Panksepp J (2000) Anticipation of rewarding electrical brain stimulation evokes ultrasonic vocalization in rats. Behav Neurosci 114:320–327CrossRefPubMedGoogle Scholar
  12. Burdgorf J, Knutson B, Panksepp J, Ikemoto S (2001) Nucleus accumbens amphetamine microinjections unconditionally elicit 50-kHz ultrasonic vocalizations in rats. Behav Neurosci 115:940–944CrossRefGoogle Scholar
  13. Burgdorf J, Panksepp J, Brudzynski SM, Beinfeld MC, Cromwell HC, Kroes RA, Moskal JR (2009) The effects of selective breeding for differential rates of 50-kHz ultrasonic vocalizations on emotional behavior in rats. Dev Psychobiol 51:34–46CrossRefPubMedGoogle Scholar
  14. Burgdorf J, Panksepp J, Moskal JR (2011) Frequency-modulated 50 kHz ultrasonic vocalizations: a tool for uncovering the molecular substrates of positive affect. Neurosci Biobehav Rev 35:1831–1836CrossRefPubMedGoogle Scholar
  15. Burgdorf J, Moskal JR, Brudzynski SM, Panksepp J (2013) Rats selectively bred for low levels of play-induced 50 kHz vocalizations as a model for autism spectrum disorders: a role for NMDA receptors. Behav Brain Res 251:18–24CrossRefPubMedPubMedCentralGoogle Scholar
  16. Burgdorf J, Wood PL, Kroes RA, Moskal JR, Panksepp J (2007) Neurobiology of 50-kHz ultrasonic vocalizations in rats: electrode mapping, lesion, and pharmacological studies. Behav Brain Res 182:274–283CrossRefPubMedGoogle Scholar
  17. Engelhardt KA, Fuchs E, Schwarting RKW, Wöhr M (2017) Effects of amphetamine on pro-social ultrasonic communication in juvenile rats: implications for mania models. Eur Neuropsychopharmacol 27:261–273CrossRefPubMedGoogle Scholar
  18. Garcia EJ, Cain ME (2016) Novelty response and 50 kHz ultrasonic vocalizations: differential prediction of locomotor and affective response to amphetamine in Sprague-Dawley rats. Psychopharmacology 233:625–637CrossRefPubMedGoogle Scholar
  19. Garcia EJ, McCowan TJ, Cain ME (2015) Harmonic and frequency modulated ultrasonic vocalizations reveal differences in conditioned and unconditioned reward processing. Behav Brain Res 287:207–214CrossRefPubMedGoogle Scholar
  20. Hutson PH, Tarazi FI, Madhou M, Slawecki C, Patkar AA (2014) Preclinical pharmacology of amphetamine: implications for the treatment of neuropsychiatric disorders. Pharmacol Ther 143:253–264CrossRefPubMedGoogle Scholar
  21. Knutson B, Burgdorf J, Panksepp J (1998) Anticipation of play elicits high-frequency ultrasonic vocalizations in young rats. J Comp Psychol 112:65–73CrossRefPubMedGoogle Scholar
  22. Kõiv K, Metelitsa M, Vares M, Tiitsaar K, Raudkivi K, Jaako K, Vulla K, Shimmo R, Harro J (2016) Chronic variable stress prevents amphetamine-elicited 50-kHz calls in rats with low positive affectivity. Eur Neuropsychopharmacol 26:631–643CrossRefPubMedGoogle Scholar
  23. Lucki I (1983) Rate-dependent effects of amphetamine on responding under random-interval schedules of reinforcement in the rat. Pharmacol Biochem Behav 18:195–201CrossRefPubMedGoogle Scholar
  24. Lukas M, Wöhr M (2015) Endogenous vasopressin, innate anxiety, and the emission of pro-social 50-kHz ultrasonic vocalizations during social play behavior in juvenile rats. Psychoneuroendocrinology 56:35–44CrossRefPubMedGoogle Scholar
  25. Mällo T, Matrov D, Herm L, Kõiv K, Eller M, Rinken A, Harro J (2007) Tickling-induced 50-kHz ultrasonic vocalization is individually stable and predicts behaviour in tests of anxiety and depression in rats. Behav Brain Res 184:57–71CrossRefPubMedGoogle Scholar
  26. Mällo T, Matrov D, Kõiv K, Harro J (2009) Effect of chronic stress on behavior and cerebral oxidative metabolism in rats with high or low positive affect. Neuroscience 164:963–974CrossRefPubMedGoogle Scholar
  27. Mu P, Fuchs T, Saal DB, Sorg BA, Dong Y, Panksepp J (2009) Repeated cocaine exposure induces sensitization of ultrasonic vocalization in rats. Neurosci Lett 453:31–35CrossRefPubMedPubMedCentralGoogle Scholar
  28. Mu P, Moyer JT, Ishikawa M, Zhang Y, Panksepp J, Sorg BA, Schlüter OM, Dong Y (2010) Exposure to cocaine dynamically regulates the intrinsic membrane excitability of nucleus accumbens neurons. J Neurosci 30:3689–3699CrossRefPubMedPubMedCentralGoogle Scholar
  29. Natusch C, Schwarting RKW (2010) Using bedding in a test environment critically affects 50-kHz ultrasonic vocalizations in laboratory rats. Pharmacol Biochem Behav 96:251–259CrossRefPubMedGoogle Scholar
  30. Panksepp J, Burgdorf J (2000) 50-kHz chirping (laughter?) in response to conditioned and unconditioned tickle-induced reward in rats: effects of social housing and genetic variables. Behav Brain Res 115:25–38CrossRefPubMedGoogle Scholar
  31. Panksepp J, Burgdorf J, Gordon N (2001) Towards a genetics of joy: breeding rats for “laughter”. In: Kaszniak A (ed) Emotions, Qualia, and Consciousness. Singapore, World Scientific:  https://doi.org/10.1142/9789812810687_0012
  32. Pereira M, Andreatini R, Schwarting RKW, Brenes JC (2014) Amphetamine-induced appetitive 50-kHz calls in rats: a marker of affect in mania? Psychopharmacology 231:2567–2577CrossRefPubMedGoogle Scholar
  33. Rygula R, Pluta H, Popik P (2012) Laughing rats are optimistic. PLoS One 7(12):e51959.  https://doi.org/10.1371/journal.pone.0051959 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301:805–809CrossRefPubMedGoogle Scholar
  35. Scardochio T, Trujillo-Pisanty I, Conover K, Shizgal P, Clarke PB (2015) The effects of electrical and optical stimulation of midbrain dopaminergic neurons on rat 50-kHz ultrasonic vocalizations. Front Behav Neurosci 9:331.  https://doi.org/10.3389/fnbeh.2015.00331 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Schwarting RKW, Jegan N, Wöhr M (2007) Situational factors, conditions and individual variables which can determine ultrasonic vocalizations in male adult Wistar rats. Behav Brain Res 182:208–222CrossRefPubMedGoogle Scholar
  37. Seffer D, Rippberger H, Schwarting RKW, Wöhr M (2015) Pro-social 50-kHz ultrasonic communication in rats: post-weaning but not post-adolescent social isolation leads to social impairments—phenotypic rescue by re-socialization. Front Behav Neurosci 9:102.  https://doi.org/10.3389/fnbeh.2015.00102 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Seffer D, Schwarting RKW, Wöhr M (2014) Pro-social ultrasonic communication in rats: insights from playback studies. J Neurosci Methods 234:73–81CrossRefPubMedGoogle Scholar
  39. Taracha E, Hamed A, Krząścik P, Lehner M, Skórzewska A, Plaźnik A, Chaprusta SJ (2012) Inter-individual diversity and intra-individual stability of amphetamine-induced sensitization of frequency-modulated 50-kHz vocalization in Sprague–Dawley rats. Psychopharmacology 222:619–632CrossRefPubMedPubMedCentralGoogle Scholar
  40. Taracha E, Kaniuga E, Chrapusta SJ, Maciejak P, Śliwa L, Hamed A, Krząścik P (2014) Diverging frequency-modulated 50-kHz vocalization, locomotor activity and conditioned place preference effects in rats given repeated amphetamine treatment. Neuropharmacology 83:128–136CrossRefPubMedGoogle Scholar
  41. Taracha E, Kaniuga E, Wyszogrodzka E, Płaźnik A, Stefański R, Chrapusta SJ (2016) Poor sensitization of 50-kHz vocalization response to amphetamine predicts rat susceptibility to self-administration of the drug. Psychopharmacology 233:2827–2840CrossRefPubMedPubMedCentralGoogle Scholar
  42. Thompson B, Leonard KC, Brudzynski SM (2006) Amphetamine-induced 50 kHz calls from rat nucleus accumbens: a quantitative mapping study and acoustic analysis. Behav Brain Res 168:64–73CrossRefPubMedGoogle Scholar
  43. van der Poel AM, Noach EJ, Miczek KA (1989) Temporal patterning of ultrasonic distress calls in the adult rat: effects of morphine and benzodiazepines. Psychopharmacology 97:147–148CrossRefPubMedGoogle Scholar
  44. Van Eukhuizen J, Janowski DS, Olivier B, Minassian A, Perry W, Young JW, Geyer MA (2015) The catecholaminergic–cholinergic balance hypothesis of bipolar disorder revisited. Eur J Pharmacol 753:114–126CrossRefGoogle Scholar
  45. Webber ES, Harmon KM, Beckwith TJ, Peña S, Burgdorf J, Panksepp J, Cromwell HC (2012) Selective breeding for 50 kHz ultrasonic vocalization emission produces alterations in the ontogeny and regulation of rough-and-tumble play. Behav Brain Res 229:138–144CrossRefPubMedGoogle Scholar
  46. Wendler E, de Souza CP, Vecchia DD, Kanazawa LKS, de Almeida Soares Hocayen P, Wöhr M, Schwarting RKW, Andreatini R (2016) Evaluation of 50-kHz ultrasonic vocalizations in animal models of mania: ketamine and lisdexamfetamine-induced hyperlocomotion in rats. Eur Neuropsychopharmacol 26:1900–1908CrossRefPubMedGoogle Scholar
  47. Willuhn I, Tose A, Wanat MJ, Hart AS, Hollon NG, Phillips PE, Schwarting RKW, Wöhr M (2014) Phasic dopamine release in the nucleus accumbens in response to pro-social 50 kHz ultrasonic vocalizations in rats. J Neurosci 34:10616-10623CrossRefPubMedPubMedCentralGoogle Scholar
  48. Wöhr M, Borta A, Schwarting RKW (2005) Overt behavior and ultrasonic vocalization in a fear conditioning paradigm: a dose-response study in the rat. Neurobiol Learn Mem 84:228–240CrossRefPubMedGoogle Scholar
  49. Wöhr M, Houx B, Schwarting RKW, Spruijt B (2008) Effects of experience and context on 50-kHz vocalizations in rats. Physiol Behav 93:766–776CrossRefPubMedGoogle Scholar
  50. Wöhr M, Kehl M, Borta A, Schänzer A, Schwarting RKW, Höglinger GU (2009) New insights into the relationship of neurogenesis and affect: tickling induces hippocampal cell proliferation in rats emitting appetitive 50-kHz ultrasonic vocalizations. Neuroscience 163:1024–1030CrossRefPubMedGoogle Scholar
  51. Wöhr M, Rippberger H, Schwarting RKW, van Gaalen MM (2015) Critical involvement of 5-HT2C receptor function in amphetamine-induced 50-kHz ultrasonic vocalizations in rats. Psychopharmacology 232:1817–1829CrossRefPubMedGoogle Scholar
  52. Wöhr M, Schwarting RKW (2007) Ultrasonic communication in rats: can playback of 50-kHz calls induce approach behavior? PLoS One 2(12):e1365.  https://doi.org/10.1371/journal.pone.0001365 CrossRefPubMedPubMedCentralGoogle Scholar
  53. Wöhr M, Schwarting RKW (2009) Ultrasonic communication in rats: effects of morphine and naloxone on vocal and behavioral responses to playback of 50-kHz vocalizations. Pharmacol Biochem Behav 94:285–295CrossRefPubMedGoogle Scholar
  54. Wöhr M, Schwarting RKW (2012) Testing social acoustic memory in rats: effects of stimulus configuration and long-term memory on the induction of social approach behavior by appetitive 50-kHz ultrasonic vocalizations. Neurobiol Learn Mem 98:154–164CrossRefPubMedGoogle Scholar
  55. Wöhr M, Schwarting RKW (2013) Affective communication in rodents: ultrasonic vocalizations as a tool for research on emotion and motivation. Cell Tissue Res. 354:81–97CrossRefPubMedGoogle Scholar
  56. Wright JM, Gourdon JC, Clarke PBS (2010) Identification of multiple call categories within the rich repertoire of adult rat 50-kHz ultrasonic vocalizations: effects of amphetamine and social context. Psychopharmacology 211:1–13CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Behavioral Neuroscience, Experimental and Biological PsychologyPhilipps-University of MarburgMarburgGermany

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