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Cocaine deprivation effect: cue abstinence over weekends boosts anticipatory 50-kHz ultrasonic vocalizations in rats.

ABSTRACT: 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.

SUBMITTER: Maier EY

PROVIDER: S-EPMC3969444 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Cocaine deprivation effect: cue abstinence over weekends boosts anticipatory 50-kHz ultrasonic vocalizations in rats.

Maier Esther Y EY Ahrens Allison M AM Ma Sean T ST Schallert Timothy T Duvauchelle Christine L CL

Behavioural brain research 20100512 1

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 e ...[more]

PMID: 20470830

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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.

Project description:RationaleAdult rats emit ultrasonic vocalizations (USVs) at around 50-kHz; these commonly occur in contexts that putatively engender positive affect. While several reports indicate that dopaminergic (DAergic) transmission plays a role in the emission of 50-kHz calls, the pharmacological evidence is mixed. Different modes of dopamine (DA) release (i.e., tonic and phasic) could potentially explain this discrepancy.ObjectiveTo investigate the potential role of phasic DA release in 50-kHz call emission.MethodsIn Experiment 1, USVs were recorded in adult male rats following unexpected electrical stimulation of the medial forebrain bundle (MFB). In parallel, phasic DA release in the nucleus accumbens (NAcc) was recorded using fast-scan cyclic voltammetry. In Experiment 2, USVs were recorded following response-contingent or non-contingent optogenetic stimulation of midbrain DAergic neurons. Four 20-s schedules of optogenetic stimulation were used: fixed-interval, fixed-time, variable-interval, and variable-time.ResultsBrief electrical stimulation of the MFB increased both 50-kHz call rate and phasic DA release in the NAcc. During optogenetic stimulation sessions, rats initially called at a high rate comparable to that observed following reinforcers such as psychostimulants. Although optogenetic stimulation maintained reinforced responding throughout the 2-h session, the call rate declined to near zero within the first 30 min. The trill call subtype predominated following both electrical and optical stimulation.ConclusionThe occurrence of electrically-evoked 50-kHz calls, time-locked to phasic DA (Experiment 1), provides correlational evidence supporting a role for phasic DA in USV production. However, in Experiment 2, the temporal dissociation between calling and optogenetic stimulation of midbrain DAergic neurons suggests that phasic mesolimbic DA release is not sufficient to produce 50-kHz calls. The emission of the trill subtype of 50-kHz calls potentially provides a marker distinguishing positive affect from positive reinforcement.

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.

Project description:Social animals tend to possess an elaborate vocal communication repertoire, and rats are no exception. Rats utilize ultrasonic vocalizations (USVs) to communicate information about a wide range of socially relevant cues, as well as information regarding the valence of the behavior and/or surrounding environment. Both quantitative and qualitative acoustic properties of these USVs are thought to communicate context-specific information to conspecifics. Rat USVs have been broadly categorized into 22 and 50 kHz call categories, which can be further classified into subtypes based on their sonographic features. Recent research indicates that the 50 kHz calls and their various subtype profiles may be related to the processing of social and non-social rewards. However, only a handful of studies have investigated USV elicitation in the context of both social and non-social rewards. Here, we employ a novel behavioral paradigm, the social-sucrose preference test, that allowed us to measure rats' vocal responses to both non-social (i.e., 2, 5, and 10% sucrose) and social reward (interact with a Juvenile rat), presented concurrently. We analyzed adult male Long-Evans rats' vocal responses toward social and non-social rewards, with a specific focus on 50 kHz calls and their 14 subtypes. We demonstrate that rats' preference and their vocal responses toward a social reward were both influenced by the concentration of the non-social reward in the maze. In other words, rats showed a trade-off between time spent with non-social or social stimuli along with increasing concentrations of sucrose, and also, we found a clear difference in the emission of flat and frequency-modulated calls in the social and non-social reward zones. Furthermore, we report that the proportion of individual subtypes of 50 kHz calls, as well as the total USV counts, showed variation across different types of rewards as well. Our findings provide a thorough overview of rat vocal responses toward non-social and social rewards and are a clear depiction of the variability in the rat vocalization repertoire, establishing the role of call subtypes as key players driving context-specific vocal responses of rats.

Dataset Information

Cocaine deprivation effect: cue abstinence over weekends boosts anticipatory 50-kHz ultrasonic vocalizations in rats.

Publications

Cocaine deprivation effect: cue abstinence over weekends boosts anticipatory 50-kHz ultrasonic vocalizations in rats.

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