Cortical theta oscillations and 50-kHz ultrasonic vocalizations in response to tactile reward indicate positive emotion in rats.

Rats emit 50-kHz ultrasonic vocalizations (USVs), which reflect positive affective states. Rhythmic stroking increases 50-kHz USVs via the mesolimbic dopaminergic system. However, little is known about the effect of tactile reward on rat brain activity. This study aimed to investigate the brain activity associated with positive emotions induced by tactile stimulation using a frontoparietal electroencephalogram (EEG) as well as through the analysis of 50-kHz USVs and behavioral activity in awake rats. During rhythmic stroking, the power of the middle theta band and harmonics calls significantly increased compared with baseline. After rhythmic stroking, fast theta oscillations significantly increased but slow theta significantly decreased, with abundant frequency-modulated (FM) calls. Light touch stimulation increased the fast theta power but decreased FM calls. However, there was no significant difference in behavior after stimulation with rhythmic stroking or light touch. These results suggest that the characteristic brain theta oscillations and 50-kHz USV profiles induced by tactile reward can detect positive affective states in rats.

Harmonics and frequency-modulated calls indicate different motivational states in rats.

Rats emit 50-kHz ultrasonic vocalizations (USVs) via the accumbal dopaminergic system in response to rhythmic stroking (RS). However, it is unknown whether RS can lead to approach behavior, which is a reliable marker of positive affective states. To assess the effects of RS on the behavioral response and its correlation with call subtypes, we measured the total number of 50-kHz USVs (overall and within call subtypes) and approach behavior in response to RS. Rats were randomly divided into two equal groups. One group received RS and the control group received light touch (LT). RS stimulation was administered for 30 s once a day for 7 consecutive days, and USVs were recorded immediately before, during, and after stimulation. RS induced 50-kHz USVs from day 1 and led to quick approach on day 2 and after. However, those responses were absent in the LT group. Specific frequency-modulated (FM) calls observed after RS were significantly correlated with approach latency. These results suggest that RS has rewarding effects, and the specific FM calls observed immediately after RS can be used as indices of innate positive reinforcement.

Simultaneous antagonism of dopamine D1/D2/D3 receptor in the NAc reduces 50-kHz ultrasonic calls in response to rhythmic tactile stroking.

Tactile stimulation such as rhythmic stroking elicits 50-kHz ultrasonic vocalizations (USVs) in rats that are thought to reflect positive affective states. Dopaminergic neurotransmission in the nucleus accumbens (NAc) is required for tactile reward-induced 50-kHz USVs; however, it is still unknown whether the accumbal dopaminergic system differentially modulates 50-kHz USV call subtypes induced by rhythmic stroking. We therefore examined both total and categorized 50-kHz USV rate, peak frequency, and duration under dopamine (DA) receptor antagonism in the NAc shell. Bilateral injection of the D1 receptor antagonist SCH 23390 (500 ng/side) plus the D2/D3 receptor antagonist raclopride (25 µg/side) significantly reduced the number of predominantly flat calls with harmonics during stimulation and the number of frequency-modulated (FM) calls after stimulation. In contrast, there were no substantial changes in total and categorized 50-kHz USVs mean peak frequencies and call durations. Therefore, emission of different subtypes of 50-kHz USVs may be differently regulated by dopaminergic transmission. The 50-kHz harmonics and FM USVs induced by rhythmic stroking may be useful behavioral markers for tactile reward in rats.

Stroking stimulation of the skin elicits 50-kHz ultrasonic vocalizations in young adult rats.

The present study aimed to clarify if stroking stimulation of the skin produces positive emotion in rats. 50-kHz ultrasonic vocalizations (USVs) were recorded as an index of the positive emotion. Stroking stimulation was applied to the ventral, dorsal, or head region of the body while the rat was in a vertical holding condition. Rats emit abundant 50-kHz USVs in response to stroking, and the number of the USVs was not different among these three stimulated regions. Other stimulations, such as light touching of the abdominal area, swinging of the body back and forth, or stroking of the external genitalia under vertical holding condition, produced significantly less 50-kHz USVs. Furthermore, different call subtypes were observed during and after stroking of the ventral region. In particular, "Trill" calls, a representative index of positive emotion, were dominant after stimulation. These results suggest that stroking of the skin induces positive emotional states.

Somatosensory regulation of serotonin release in the central nucleus of the amygdala is mediated via corticotropin releasing factor and gamma-aminobutyric acid in the dorsal raphe nucleus.

Noxious cutaneous stimulation increases, whereas innocuous cutaneous stimulation decreases serotonin (5-HT) release in the central nucleus of the amygdala (CeA) in anesthetized rats. In the present study, we investigated the contribution of corticotropin releasing factor (CRF) receptors and gamma-aminobutyric acid (GABA) receptors in the dorsal raphe nucleus (DRN) to those responses. Release of 5-HT in the CeA was monitored by microdialysis before and after 10-min stimulation by pinching or stroking. Increased 5-HT release in the CeA in response to pinching was abolished by CRF2 receptor antagonism in the DRN. Decreased 5-HT release in the CeA in response to stroking was abolished by either CRF1 receptor antagonism or GABAA receptor antagonism in the DRN. These results suggest that opposite responses of 5-HT release in the CeA to noxious versus innocuous stimulation of the skin are due to separate contributions of CRF2, CRF1 and GABAA receptors in the DRN.

Serotonin release in the central nucleus of the amygdala in response to noxious and innocuous cutaneous stimulation in anesthetized rats.

We investigated the effect of noxious (pinching) and innocuous (stroking) stimulation of skin on serotonin (5-HT) release in the central nucleus of the amygdala (CeA) in anesthetized rats. 5-HT in the CeA was collected by microdialysis methods. Dialysate output from consecutive 10-min periods was injected into a high-performance liquid chromatograph and 5-HT was measured with an electrochemical detector. Bilateral pinching of the back for 10 min increased 5-HT release significantly; 5-HT release was also increased with stimulation of the forelimb or hindlimb. In contrast, stroking of these areas decreased 5-HT release significantly. Furthermore, simultaneous stroking and pinching produced no change in the 5-HT release. In conclusion, the present study demonstrates that 5-HT release in the CeA is regulated by somatic afferent stimulation in a modality-dependent manner, and that innocuous stimulation can dampen the change in 5-HT release that occurs in response to noxious stimulation.

Tickling increases dopamine release in the nucleus accumbens and 50 kHz ultrasonic vocalizations in adolescent rats.

Adolescent rats emit 50 kHz ultrasonic vocalizations, a marker of positive emotion, during rough-and-tumble play or on tickling stimulation. The emission of 50 kHz ultrasonic vocalizations in response to tickling is suggested to be mediated by dopamine release in the nucleus accumbens; however, there is no direct evidence supporting this hypothesis. The present study aimed to elucidate whether play behavior (tickling) in adolescent rats can trigger dopamine release in the nucleus accumbens with hedonic 50 kHz ultrasonic vocalizations. The effect of tickling stimulation was compared with light-touch stimulation, as a discernible stimulus. We examined 35-40-day-old rats, which corresponds to the period of midadolescence. Tickling stimulation for 5 min significantly increased dopamine release in the nucleus accumbens (118±7% of the prestimulus control value). Conversely, light-touch stimulation for 5 min did not significantly change dopamine release. In addition, 50 kHz ultrasonic vocalizations were emitted during tickling stimulation but not during light-touch stimulation. Further, tickling-induced 50 kHz ultrasonic vocalizations were significantly blocked by the direct application of SCH23390 (D1 receptor antagonist) and raclopride (D2/D3 receptor antagonist) into the nucleus accumbens. Our study demonstrates that tickling stimulation in adolescent rats increases dopamine release in the nucleus accumbens, leading to the generation of 50 kHz ultrasonic vocalizations.

Tactile skin stimulation increases dopamine release in the nucleus accumbens in rats.

We investigated the effect of mild (non-noxious) tactile stimulation (stroking) of skin on dopamine (DA) release in the nucleus accumbens (NAc) of rats. A coaxial microdialysis probe was stereotaxically implanted in the NAc and perfused with modified Ringer's solution. Dialysate output from consecutive 5-min periods was injected into a high-performance liquid chromatograph and DA was measured using an electrochemical detector. Bilateral tactile stimulation of the back for 5 min significantly increased DA release in conscious and anesthetized animals. Increased DA release was observed by stimulation of the contralateral, but not ipsilateral, back. DA secretion was also increased with stimulation of the forelimb, hindlimb, and abdomen. These effects were abolished after lesioning the ventral tegmental area (VTA). In contrast, noxious stimulation (pinching) of these areas had no effect on DA secretion. In conclusion, innocuous mechanical stimulation of the skin increases DA release in the contralateral NAc via the VTA.

Electro-acupuncture improves responsiveness to insulin via excitation of somatic afferent fibers in diabetic rats.

The effects of electro-acupuncture (EA) on plasma concentration of glucose and on responsiveness to insulin were examined in an animal model of diabetes, the streptozotocin-treated rat. Two weeks after treatment with streptozotocin, rats were anesthetized with urethane-chloralose and subjected to the EA for 10 min delivered to the tibialis anterior muscle of one side. The stimulation produced no significant changes in plasma glucose concentration. In contrast, EA increased the response of plasma glucose to insulin (0.2 U kg(-1)). The effect of EA on the responsiveness to insulin was abolished by section of both sciatic and femoral nerves ipsilateral to the side of the EA. These results show that EA in diabetic rats has no effect on plasma glucose concentration while it augments the responsiveness to insulin, and we show that this occurs via a mechanism that involves the somatic afferent nerves.