Phasic dopamine release in the nucleus accumbens in response to pro-social 50 kHz ultrasonic vocalizations in rats

Abstract

Rats emit ultrasonic vocalizations (USVs) that are thought to serve as situation-dependent affective signals and accomplish important communicative functions. In appetitive situations, rats produce 50 kHz USVs, whereas 22 kHz USVs occur in aversive situations. Reception of 50 kHz USVs induces social approach behavior, while 22 kHz USVs lead to freezing behavior. These opposite behavioral responses are paralleled by distinct brain activation patterns, with 50 kHz USVs, but not 22 kHz USVs, activating neurons in the nucleus accumbens (NAcc). The NAcc mediates appetitive behavior and is critically modulated by dopaminergic afferents that are known to encode the value of reward. Therefore, we hypothesized that 50 kHz USVs, but not 22 kHz USVs, elicit NAcc dopamine release. While recording dopamine signaling with fast-scan cyclic voltammetry, freely moving rats were exposed to playback of four acoustic stimuli via an ultrasonic speaker in random order: (1) 50 kHz USVs, (2) 22 kHz USVs, (3) time- and amplitude-matched white noise, and (4) background noise. Only presentation of 50 kHz USVs induced phasic dopamine release and elicited approach behavior toward the speaker. Both of these effects, neurochemical and behavioral, were most pronounced during initial playback, but then declined rapidly with subsequent presentations, indicating a close temporal relationship between the two measures. Moreover, the magnitudes of these effects during initial playback were significantly correlated. Collectively, our findings show that NAcc dopamine release encodes pro-social 50 kHz USVs, but not alarming 22 kHz USVs. Thus, our results support the hypothesis that these call types are processed in distinct neuroanatomical regions and establish a functional link between pro-social communicative signals and reward-related neurotransmission.

Keywords: dopamine; fast-scan cyclic voltammetry; nucleus accumbens; social behavior; ultrasonic communication.

Figure 1.

Acoustic stimuli used for playback. Exemplary spectrograms of (A) 50 kHz USVs, (B) 22 kHz USVs, (C) time- and amplitude-matched white noise (NOISE), and (D) background noise (BACKGROUND). E, Acoustic stimuli were presented repeatedly for 15 s in random order by an ultrasonic loudspeaker (ScanSpeak; Avisoft Bioacoustics).

Figure 2.

Behavioral responses to playback of acoustic stimuli. A, Change from baseline in locomotion measured by counting the number of quadrant line crossings, and B, Change from baseline in the time spent proximal to the ultrasonic loudspeaker in response to the first six presentations of 50 kHz USVs on the first day of the experiment; *p < 0.050, 50 kHz USVs compared with baseline. C, Change in locomotion, and D, change in the time spent proximal to the ultrasonic loudspeaker in response to the first two presentations of 50 and 22 kHz USVs, time- and amplitude-matched white noise (NOISE), and background noise (BACKGROUND) on the first day of the experiment; *p < 0.050, 50 kHz USVs compared with all other acoustic stimuli. Data are presented as differences from baseline (baseline subtraction); mean + SEM (n = 12 rats for each presentation).

Figure 3.

Changes in dopamine release in the NAcc in response to playback of acoustic stimuli. A, Exemplary pseudocolor plot of the change in phasic dopamine release associated with a single playback presentation of 50 kHz USVs. B, Exemplary pseudocolor plot of the change in phasic dopamine release associated with a single playback presentation of 22 kHz USVs. C, Change in dopamine concentration and cyclic voltammograms (inset) for representative current fluctuations shown in A for the period 10 s before the beginning of the 50 kHz USV presentation (left dashed line), during the 15 s presentation (yellow box), and 10 s after the offset (right dashed line). D, Change in dopamine concentration and cyclic voltammograms (inset) for representative current fluctuations shown in B for the period 10 s before the beginning of the 22 kHz USV presentation (left dashed line), during the 15 s presentation (yellow box), and 10 s after the offset (right dashed line).

Figure 4.

Average changes in dopamine release in the NAcc in response to playback of acoustic stimuli, namely the first two presentations of (A) 50 kHz USVs, (B) 22 kHz-USVs, (C) time- and amplitude-matched white noise (NOISE), and (D) background noise (BACKGROUND) on the first day of the experiment. E, The increase in dopamine release during the 50 kHz USV playback is significantly greater than during the other acoustic stimuli. F, The increase in dopamine release during 50 kHz USV playback is significantly correlated with approach behavior toward the sound source. G, The increase in dopamine release during playback of the first two 50 kHz USVs is significantly greater than subsequent presentations. H, Average change in dopamine release in the NAcc in response to playback of acoustic stimuli, namely the first two presentations of 50 kHz USVs on the second day of the experiment (n = 10); **p < 0.010. Data are presented as differences from baseline (baseline subtraction); mean + SEM (n = 12 rats for each presentation unless indicated otherwise).