Limited generalizability, pharmacological modulation, and state-dependency of habituation towards pro-social 50-kHz calls in rats.
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ABSTRACT:
SUBMITTER: Berz A
PROVIDER: S-EPMC8102916 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Positive animal emotion (affect) is a key component of good animal welfare [1] and plays an important role in stress-coping and resilience [2]. Methods for reliably inducing and measuring positive affect are critical, but both have been limited in availability. In rats, one promising way of inducing positive affective states is by human-simulated rough and tumble play or 'tickling' [3,4]. However, in humans tickling induces both pleasure and displeasure, and neither an established non-verbal indicator of positive affect, the Duchenne smile, nor laughter detects this variation [5,6]. Rats also show individual differences in response to tickling [7], and this variation needs to be readily quantified if we are to ensure that tickling is only implemented where it generates positive affect. Here, we use a validated and objective measure of affective valence, the affective bias test [8], to show that 50 kHz ultrasonic vocalizations provide a quantifiable and graded measure of positive affect that accurately reflects the positive state induced by this human-rat interaction.
| S-EPMC7533284 | biostudies-literature
Project description:Rats emit distinct types of ultrasonic vocalizations, which differ depending on age, the subject's current state and environmental factors. Since it was shown that 50-kHz calls can serve as indices of the animal's positive subjective state, they have received increasing experimental attention, and have successfully been used to study neurobiological mechanisms of positive affect. However, it is likely that such calls do not only reflect a positive affective state, but that they also serve a communicative purpose. Actually, rats emit the highest rates of 50-kHz calls typically during social interactions, like reproductive behavior, juvenile play and tickling. Furthermore, it was recently shown that rats emit 50-kHz calls after separation from conspecifics. The aim of the present study was to test the communicative value of such 50-kHz calls. In a first experiment, conducted in juvenile rats situated singly on a radial maze apparatus, we showed that 50-kHz calls can induce behavioral activation and approach responses, which were selective to 50-kHz signals, since presentation of 22-kHz calls, considered to be aversive or threat signals, led to behavioral inhibition. In two other experiments, we used either natural 50-kHz calls, which had been previously recorded from other rats, or artificial sine wave stimuli, which were identical to these calls with respect to peak frequency, call length and temporal appearance. These signals were presented to either juvenile (Exp. 2) or adult (Exp. 3) male rats. Our data clearly show that 50-kHz signals can induce approach behavior, an effect, which was more pronounced in juvenile rats and which was not selective to natural calls, especially in adult rats. The recipient rats also emitted some 50-kHz calls in response to call presentation, but this effect was observed only in adult subjects. Together, our data show that 50-kHz calls can serve communicative purposes, namely as a social signal, which increases the likelihood of approach in the recipient conspecific.
| S-EPMC2137933 | biostudies-literature
Project description:Rats are highly social animals known to communicate with ultrasonic vocalizations (USV) of different frequencies. Calls around 50 kHz are thought to represent a positive affective state, whereas calls around 22 kHz are believed to serve as alarm or distress calls. During playback of natural 50-kHz USV, rats show a reliable and strong social approach response toward the sound source. While this response has been studied in great detail in numerous publications, little is known about the emission of USV in response to natural 50-kHz USV playback. To close this gap, we capitalized on three data sets previously obtained and analyzed USV evoked by natural 50-kHz USV playback in male juvenile rats. We compared different rat stocks, namely Wistar (WI) and Sprague-Dawley (SD) and investigated the pharmacological treatment with the dopaminergic D2 receptor antagonist haloperidol. These response calls were found to vary broadly inter-individually in numbers, mean peak frequencies, durations and frequency modulations. Despite the large variability, the results showed no major differences between experimental conditions regarding call likelihood or call parameters, representing a robust phenomenon. However, most response calls had clearly lower frequencies and were longer than typical 50-kHz calls, i.e., around 30 kHz and lasting generally around 0.3 s. These calls resemble aversive 22-kHz USV of adult rats but were of higher frequencies and shorter durations. Moreover, blockade of dopamine D2 receptors did not substantially affect the emission of response calls suggesting that they are not dependent on the D2 receptor function. Taken together, this study provides a detailed analysis of response calls toward playback of 50-kHz USV in juvenile WI and SD rats. This includes calls representing 50-kHz USV, but mostly calls with lower frequencies that are not clearly categorizable within the so far known two main groups of USV in adult rats. We discuss the possible functions of these response calls addressing their communicative functions like contact or appeasing calls, and whether they may reflect a state of frustration. In future studies, response calls might also serve as a new read-out in rat models for neuropsychiatric disorders, where acoustic communication is impaired, such as autism spectrum disorder.
| S-EPMC8797927 | biostudies-literature
Project description:The control of mammalian pests relies heavily on the use of pesticides that are often avoided and are not species-specific. These problems are particularly acute for pesticides used to control rats (Rattus spp.). The efficacy and targeting of control could be improved by attracting animals to control measures using species-specific cues. One cue that has the potential to attract rats is the 50 kHz calls they emit in positive social situations. Here we test the potential of these rat calls as a species-specific attractant by examining the response of laboratory rats (Rattus norvegicus; n = 48) and non-target bank voles (Myodes glareolus; n = 16) to 50 kHz calls from either sex in a compartmentalised laboratory arena. Sounds of rat movement and white noise acted as control treatments, with each sound tested against a silent control in the opposite side of the arena. When sound cues were played above an empty bait box, rats were attracted to spend time close to 50 kHz rat calls, climbing on top of boxes, regardless of the sex of subject or caller. When either 50 kHz rat calls or rat movement sounds were played inside an empty bait box, rats of both sexes spent 3-4 fold more time inside boxes and visited more frequently. Rats were not attracted by intermittent white noise. Bank voles were neither attracted to, nor avoided, 50 kHz rat calls played inside empty bait boxes. Our findings show that 50 kHz rat calls are an effective attractant for rats of both sexes under laboratory conditions, while not attracting non-target bank voles. These calls are strong candidates for providing a species-specific lure that may be attractive even in the absence of food bait, but further trials will be needed to assess their efficacy under field conditions.
| S-EPMC6453455 | biostudies-literature
Project description:The cross-disorder risk gene CACNA1C is strongly implicated in multiple neuropsychiatric disorders, including autism spectrum disorder (ASD), bipolar disorder (BPD) and schizophrenia (SCZ), with deficits in social functioning being common for all major neuropsychiatric disorders. In the present study, we explored the role of Cacna1c in regulating disorder-relevant behavioral phenotypes, focusing on socio-affective communication after weaning during the critical developmental period of adolescence in rats. To this aim, we used a newly developed genetic Cacna1c rat model and applied a truly reciprocal approach for studying communication through ultrasonic vocalizations, including both sender and receiver. Our results show that a deletion of Cacna1c leads to deficits in social behavior and pro-social 50-kHz ultrasonic communication in rats. Reduced levels of 50-kHz ultrasonic vocalizations emitted during rough-and-tumble play may suggest that Cacna1c haploinsufficient rats derive less reward from playful social interactions. Besides the emission of fewer 50-kHz ultrasonic vocalizations in the sender, Cacna1c deletion reduced social approach behavior elicited by playback of 50-kHz ultrasonic vocalizations. This indicates that Cacna1c haploinsufficiency has detrimental effects on 50-kHz ultrasonic communication in both sender and receiver. Together, these data suggest that Cacna1c plays a prominent role in regulating socio-affective communication in rats with relevance for ASD, BPD and SCZ.This article has an associated First Person interview with the first author of the paper.
| S-EPMC6031367 | biostudies-literature
Project description:Rats are highly social animals and social play during adolescence has an important role for social development, hence post-weaning social isolation is widely used to study the adverse effects of juvenile social deprivation and to induce behavioral phenotypes relevant to neuropsychiatric disorders, like schizophrenia. Communication is an important component of the rat's social behavior repertoire, with ultrasonic vocalizations (USV) serving as situation-dependent affective signals. High-frequency 50-kHz USV occur in appetitive situations and induce approach behavior, supporting the notion that they serve as social contact calls; however, post-weaning isolation effects on the behavioral changes displayed by the receiver in response to USV have yet to be studied. We therefore investigated the impact of post-weaning isolation on socio-affective information processing as assessed by means of our established 50-kHz USV radial maze playback paradigm. We showed that post-weaning social isolation specifically affected the behavioral response to playback of pro-social 50-kHz but not alarm 22-kHz USV. While group-housed rats showed the expected preference, i.e., approach, toward 50-kHz USV, the response was even stronger in short-term isolated rats (i.e., 1 day), possibly due to a higher level of social motivation. In contrast, no approach was observed in long-term isolated rats (i.e., 4 weeks). Importantly, deficits in approach were reversed by peer-mediated re-socialization and could not be observed after post-adolescent social isolation, indicating a critical period for social development during adolescence. Together, these results highlight the importance of social experience for affiliative behavior, suggesting a critical involvement of play behavior on socio-affective information processing in rats.
| S-EPMC4416445 | biostudies-literature
Project description:In drug dependence studies, rats are often tested daily with short breaks (such as weekends) spent untested in their home cages. Research on alcohol models has suggested that breaks from continuous testing can transiently enhance self-administration (termed the "alcohol deprivation effect"). The present study explored whether the salience of cocaine-access cues is increased after skipping weekend cocaine and cue exposures. Ultrasonic vocalizations (USVs) of the 50-kHz class are emitted by rats exposed to intravenous cocaine and have been shown to increase with repeated drug exposure at the same dose level (sensitization). The present study found that over the course of several weeks of cocaine self- or yoked-administration pre-drug cues signaling forthcoming access or delivery of cocaine elicited marked amounts of anticipatory 50-kHz USVs, and that weekend deprivation from cues and cocaine exaggerated further the level of calling (more calls on Mondays compared to Fridays). Anticipatory USVs extinguished less rapidly when weekend access to unreinforced cues was denied. The results may have clinical implications, in that intermittently avoiding cues or context may enhance drug cue salience and resistance to extinction.
| S-EPMC3969444 | biostudies-literature
Project description:BackgroundApproval of drugs in chronic hepatitis C is supported by registration trials. These trials might have limited generalizability through use of strict eligibility criteria. We compared effectiveness and safety of real world hepatitis C patients eligible and ineligible for registration trials.MethodsWe performed a nationwide, multicenter, retrospective cohort study of chronic hepatitis C patients treated in the real world. We applied a combined set of inclusion and exclusion criteria of registration trials to our cohort to determine eligibility. We compared effectiveness and safety in eligible vs. ineligible patients, and performed sensitivity analyses with strict criteria. Further, we used log binomial regression to assess relative risks of criteria on outcomes.ResultsIn this cohort (n = 467) 47% of patients would have been ineligible for registration trials. Main exclusion criteria were related to hepatic decompensation and co-morbidity (cardiac disease, anemia, malignancy and neutropenia), and were associated with an increased risk for serious adverse events (RR 1.45-2.31). Ineligible patients developed significantly more serious adverse events than eligible patients (27% vs. 11%, p< 0.001). Effectiveness was decreased if strict criteria were used.ConclusionsNearly half of real world hepatitis C patients would have been excluded from registration trials, and these patients are at increased risk to develop serious adverse events. Hepatic decompensation and co-morbidity were important exclusion criteria, and were related to toxicity. Therefore, new drugs should also be studied in these patients, to genuinely assess benefits and risk of therapy in the real world population.
| S-EPMC5012685 | biostudies-literature
Project description:Background:Rats emit 50-kHz ultrasonic vocalizations (USVs) to communicate positive emotional states, and these USVs are increasingly being investigated in preclinical studies on reward and motivation. Although it is the activation of dopamine receptors that initiates the emission of 50-kHz USVs, non-dopaminergic mechanisms may modulate calling in the 50 kHz frequency band. To further elucidate these mechanisms, the present study investigated whether the pharmacological manipulation of glucocorticoid signaling influenced calling. Methods:Rats were administered corticosterone (1-5 mg/kg, s.c.), the glucocorticoid receptor antagonist mifepristone (40 or 100 mg/kg, s.c.), or the corticosterone synthesis inhibitor metyrapone (50 or 100 mg/kg, i.p.). The effects of these drugs on calling initiation and on calling recorded during nonaggressive social contacts or after the administration of amphetamine (0.25 or 1 mg/kg, i.p.) were then evaluated. Results:Corticosterone failed to initiate the emission of 50-kHz USVs and did not influence pro-social and amphetamine-stimulated calling. Similarly, mifepristone and metyrapone did not initiate calling. However, metyrapone suppressed pro-social calling and calling stimulated by a moderate dose (1 mg/kg, i.p.) of amphetamine. Conversely, mifepristone attenuated calling stimulated by a low (0.25 mg/kg, i.p.), but not moderate (1 mg/kg, i.p.), dose of amphetamine and had no influence on pro-social calling. Conclusions:The present results demonstrate that glucocorticoid signaling modulates calling in the 50 kHz frequency band only in certain conditions and suggest that mechanisms different from the inhibition of corticosterone synthesis may participate in the suppression of calling by metyrapone.
| S-EPMC5795343 | biostudies-literature
Project description:Electromechanical force derived from the soma of the outer hair cell has long been postulated as the basis of the exquisite sensitivity of the cochlea. The problem with this postulate is that the electrical source and mechanical load for the electromechanical outer hair cell might be severely attenuated and phase-shifted by the electrical impedance of the cell and the mechanical impedance of the organ of Corti, respectively. Until now, it has not been possible to experimentally derive the high-frequency electrically induced force at the reticular lamina when the cells are embedded within the organ of Corti. In the study reported here, we succeeded in determining the frequency spectrum of the force up to 50 kHz. This was achieved by measuring both the electrically induced velocity and the mechanical impedance at different radial positions on the reticular lamina without tectorial membrane and with clamped basilar membrane. Velocity was measured with a laser interferometer and impedance, with a magnetically driven atomic force cantilever. The electromechanical force, normalized to the electric current density, exhibited a broad amplitude maximum at 7-20 kHz with a quality factor, Q(3dB), of 0.6 - 0.8. The displacement response was independent of frequency up to 10-20 kHz. The force response compensates for the viscoelastic impedance of the organ of Corti, extending the amplitude response of the organ to high frequencies. It is proposed that the electrical phase response of the cell is compensated with Zwislocki's original mechanism of a parallel resonance in the tectorial membrane-stereocilia complex.
| S-EPMC535427 | biostudies-literature