Pharmacology of Ultrasonic Vocalizations in adult Rats: Significance, Call Classification and Neural Substrate

Abstract

Pharmacological studies of emotional arousal and initiation of emotional states in rats measured by their ultrasonic vocalizations are reviewed. It is postulated that emission of vocalizations is an inseparable feature of emotional states and it evolved from mother-infant interaction. Positive emotional states are associated with emission of 50 kHz vocalizations that could be induced by rewarding situations and dopaminergic activation of the nucleus accumbens and are mediated by D1, D2, and partially D3 dopamine receptors. Three biologically significant subtypes of 50 kHz vocalizations have been identified, all expressing positive emotional states: (1) flat calls without frequency modulation that serve as contact calls during social interactions; (2) frequencymodulated calls without trills that signal rewarding and significantly motivated situation; and (3) frequency-modulated calls with trills or trills themselves that are emitted in highly emotional situations associated with intensive affective state. Negative emotional states are associated with emission of 22 kHz vocalizations that could be induced by aversive situations, muscarinic cholinergic activation of limbic areas of medial diencephalon and forebrain, and are mediated by M2 muscarinic receptors. Two biologically significant subtypes of 22 kHz vocalizations have been identified, both expressing negative emotional sates: (1) long calls that serve as alarm calls and signal external danger; and (2) short calls that express a state of discomfort without external danger. The positive and negative states with emission of vocalizations are initiated by two ascending reticular activating subsystems: the mesolimbic dopaminergic subsystem as a specific positive arousal system, and the mesolimbic cholinergic subsystem as a specific negative arousal system.

Role of hypocretin/orexin receptor blockade on drug-taking and ultrasonic vocalizations (USVs) associated with low-effort self-administration of cathinone-derived 3,4-methylenedioxypyrovalerone (MDPV) in rats

“…We observed that suvorexant attenuated 50-kHz USVs during each of pre- and post-lever time-points. Our prior work shows that suvorexant pretreatment suppresses cocaine-evoked elevations in ventral striatal dopamine (Gentile et al 2017) which supports the hypothesis that mesolimbic dopamine underlies the elicitation of 50-kHz USVs (for reviews, see Barker et al 2015; Brudzynski 2015). From the three categories of call types analyzed in the present report, 50-kHz USV call type remained stable irrespective of suvorexant pre-treatment with majority of calls belonging to FM 1–2 call type which supports earlier work describing USVs associated with cocaine-paired cue presentation (Meyer et al 2012).…”

Sex‐dependent effects of Cacna1c haploinsufficiency on juvenile social play behavior and pro‐social 50‐kHz ultrasonic communication in rats

“…DA has been strongly associated with reward processing 111,112 and 50-kHz ultrasonic communication. 113,114 Importantly, DA signaling is profoundly altered in mice with genetic modifications targeting Cacna1c, 115 with evidence for sex-dependency of Cacna1c depletion effects. 12 This is in line with previous findings reporting a lack of repetitive and stereotyped patterns of behavior in Cacna1c +/− mice, as assessed by means of self-grooming 129 and marble-burying.…”

“…Interestingly, however, it was reported that Ca v 1.2 is a target of estradiol in vivo and that estradiol directly potentiates Ca 2+ influx via Ca v 1.2 through the dihydropyridine binding site 109. DA has been strongly associated with reward processing 111,112 and 50-kHz ultrasonic communication 113,114. Another potential candidate appears to be the neurotransmitter dopamine (DA).…”

USVSEG: A robust segmentation of rodents’ ultrasonic vocalization

“…On the other hand, it has been also well described that laboratory rats (Rattus norvegicus domesticus) produce USV syllables which have two predominant categories: one has a relatively higher frequency (around 50 kHz) with a few ten milliseconds in duration, and the other is in the low frequency range (~22 kHz) but much longer duration. These two USV syllables are here named as 'pleasant' and 'distress' syllables since these are generally considered to be indicators of positive and negative emotional states, respectively [6][7][8][9]. This categorization appears to be preserved in different strains of rats, though a slight difference in duration has been reported (Sales, 1979).…”

“…Perception of these call also have suggested an effect to modulate listeners' affective states [20]. Further discrimination of subcategories in the pleasant call has been studied to better know their functional difference in different situations [6][7][8][9].…”