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

Wöhr, Markus; Rippberger, Henrike; Schwarting, Rainer K.W.; Gaalen, Marcel M. van

doi:10.1007/s00213-014-3814-9

Cited by 50 publications

(48 citation statements)

References 82 publications

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“…In no instance did rats administered amphetamine or cocaine emit aversive 22 kHz USVs. Administered alone, amphetamine produced an inverted U-shaped dose response curve for the emission of ultrasonic vocalizations (data not shown) and showed 2 mg/kg to be an optimal dose for amphetamine induction of 50 kHz USV behavior as previously determined [34, 35]. Additionally, animals generally began emitting calls within five min after drug administration and continued to emit calls up to approximately 90 minutes (data not shown).…”

Section: Methodssupporting

confidence: 67%

“…Additionally, amphetamine and cocaine have different relative affinities for the DA, 5-HT and NE transporters [44]. In fact, an involvement of serotonin in the development of amphetamine-induced USV behavior has been established [35], although such involvement has not been established with cocaine. Thus, the molecular mechanisms by which amphetamine and cocaine increase synaptic dopamine level may be responsible for the distinct aspects of behavioral responses observed after both acute and repeated administration.…”

Section: Discussionmentioning

confidence: 99%

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Dopamine-sensitive signaling mediators modulate psychostimulant-induced ultrasonic vocalization behavior in rats

Williams

Undieh

2016

Behavioural Brain Research

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The mesolimbic dopamine system plays a major role in psychostimulant-induced ultrasonic vocalization (USV) behavior in rodents. Within this system, psychostimulants elevate synaptic concentrations of dopamine thereby leading to exaggerated activation of postsynaptic dopamine receptors within the D1-like and D2-like subfamilies. Dopamine receptor stimulation activate several transmembrane signaling systems and cognate intracellular mediators; downstream activation of transcription factors then conveys the information from receptor activation to appropriate modulation of cellular and physiologic functions. We previously showed that cocaine-induced USV behavior was associated with enhanced expression of the neurotrophin BDNF. Like cocaine, amphetamine also increases synaptic dopamine levels, albeit primarily through facilitating dopamine release. Therefore, in the present study we investigated whether amphetamine and cocaine similarly activate dopamine -linked signaling cascades to regulate intracellular mediators leading to induction of USV behavior. The results show that amphetamine increased the emission of 50 kHz USVs and this effect was blocked by SCH23390, a D1 receptor antagonist. Similar to cocaine, amphetamine increased BDNF protein expression in discrete brain regions, while pretreatment with K252a, a trkB neurotrophin receptor inhibitor, significantly reduced amphetamine-induced USV behavior. Inhibition of cyclic- AMP/PKA signaling with H89 or inhibition of PLC signaling with U73122 significantly blocked both the acute and subchronic amphetamine-induced USV behavior. In contrast, pharmacologic inhibition of either pathway enhanced cocaine-induced USV behavior. Although cocaine and amphetamine similarly modulate neurotrophin expression and USV, the molecular mechanisms by which these psychostimulants differentially activate dopamine receptor subtypes or other monoaminergic systems may be responsible for the distinct aspects of behavioral responses.

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Section: Methodssupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Dopamine-sensitive signaling mediators modulate psychostimulant-induced ultrasonic vocalization behavior in rats

Williams

Undieh

2016

Behavioural Brain Research

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“…Combined, these reports support that positive affective USVs are generated in part through mesolimbic DA transmission. It should be noted that a constellation of other transmitter systems have been individually implicated in the production of 50-kHz USVs including glutamatergic, noradrenergic, serotoninergic, adenosinergic and dynorphinergic transmission (Sadananda et al , 2012; Wright et al , 2012; Costa et al , 2015; Hamed et al , 2015; Wohr et al , 2015; Simola et al , 2016). As MDPV functions as both a DA and NE transport blocker, the possibility remains that positive affect elicited following MDPV administration is supported by enhanced signaling along both dopaminergic and noradrenergic transmitter systems.…”

Section: Discussionmentioning

confidence: 99%

Comparing rewarding and reinforcing properties between ‘bath salt’ 3,4‐methylenedioxypyrovalerone (MDPV) and cocaine using ultrasonic vocalizations in rats

et al. 2016

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Abuse of synthetic psychostimulants like synthetic cathinones has risen in recent years. 3,4-Methylenedioxypyrovalerone (MDPV) is one such synthetic cathinone that demonstrates a mechanism of action similar to cocaine. Compared to cocaine, MDPV is more potent at blocking dopamine and norepinephrine reuptake and is readily self-administered by rodents. The present study compared the rewarding and reinforcing properties of MDPV and cocaine using systemic injection dose-response and self-administration models. Fifty kilohertz ultrasonic vocalizations (USVs) were recorded as an index of positive affect throughout experiments. In Experiment 1, MDPV and cocaine dose-dependently elicited 50-kHz USVs upon systemic injection, but MDPV increased USVs at greater rates and with greater persistence relative to cocaine. In Experiment 2, latency to begin MDPV self-administration was shorter than latency to begin cocaine self-administration, and self-administered MDPV elicited greater and more persistent rates of 50-kHz USVs versus cocaine. MDPV-elicited 50-kHz USVs were sustained over the course of drug load-up whereas cocaine-elicited USVs waned following initial infusions. Notably, we observed a robust presence of context-elicited 50-kHz USVs from both MDPV and cocaine self-administering rats. Collectively, these data suggest that MDPV has powerfully rewarding and reinforcing effects relative to cocaine at one-tenth doses. Consistent with prior work, we additionally interpret these data in supporting that MDPV has significant abuse risk based on its potency and subjectively positive effects. Future studies will be needed to better refine therapeutic strategies targeted at reducing the rewarding effects of cathinone analogs in efforts to ultimately reduce abuse liability.

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“…Some evidence indicates that rats are biologically prepared to associate 22-kHz USVs to aversive events (Endres et al, 2007), probably through observational learning and/or auto-conditioning (Kim et al, 2010;Parsana et al, 2012b). At the neuronal level, playback of 22-kHz USVs was shown to induce increased neural activity in various brain areas associated with the processing of negative emotional stimuli, most notably the amygdala and periaqueductal grey (Sadananda et al, 2008;Parsana et al, 2012a), consistent with the idea that 22-kHz USVs serve an alarming function.Appetitive 50-kHz USVs occur mostly in social situations, such as rough-and-tumble play (e.g., Knutson et al, 1998;Kisko et al, 2015) and mating (e.g., Barfield and Thomas, 1986;Burgdorf et al, 2008), but also in response to drug of abuse, most notably the psychostimulant amphetamine (e.g., Burgdorf et al, 2001;Wöhr et al, 2015). This USV type is defined by a comparatively broad peak frequency range between 30 and 90 kHz, with most 50-kHz USVs being within 50 to 70 kHz and characterized by high levels of frequency modulation but short call durations of typically less than ß50 msec.…”

mentioning

confidence: 99%

Studying Socio‐Affective Communication in Rats through Playback of Ultrasonic Vocalizations

2016

Self Cite

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Rats are able to produce ultrasonic vocalizations (USVs). Such USVs are an important component of the rat social behavior repertoire and serve distinct communicative functions as socio-affective signals. Depending on the emotional valence of the situation, juvenile and adult rats utter (1) aversive 22-kHz USVs conveying an appeasing and/or alarming function; or (2) appetitive 50-kHz USVs, which act as social contact calls, amongst others. A 50-kHz USV radial maze playback paradigm that allows assessment of the behavioral responses displayed by the recipients in a highly standardized manner has been developed. In this newly developed paradigm, a rat is exposed individually to playback of natural 50-kHz USVs and appropriate acoustic control stimuli using an acoustic presentation system for ultrasound. By this means, it has been consistently shown that 50-kHz USVs lead to social approach behavior in the recipient, supporting the notion that they serve an affiliative function as social contact calls.

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

Abstract: 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.

Cited by 50 publications

References 82 publications

Dopamine-sensitive signaling mediators modulate psychostimulant-induced ultrasonic vocalization behavior in rats

Dopamine-sensitive signaling mediators modulate psychostimulant-induced ultrasonic vocalization behavior in rats

Comparing rewarding and reinforcing properties between ‘bath salt’ 3,4‐methylenedioxypyrovalerone (MDPV) and cocaine using ultrasonic vocalizations in rats

Studying Socio‐Affective Communication in Rats through Playback of Ultrasonic Vocalizations

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