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Environmental and Pharmacological Modulation of Amphetamine- Induced 50-kHz Ultrasonic Vocalizations in Rats.

Rippberger H, van Gaalen MM, Schwarting RK, Wohr M - Curr Neuropharmacol (2015)

Bottom Line: NA neurotransmission also regulates AMPH-induced 50-kHz USV emission given that α 1 receptor antagonists and α 2 receptor agonists exert attenuating effects.Supporting the involvement of the 5-HT system, AMPH-induced 50-kHz USV are attenuated by 5-HT2C receptor activation, whereas 5-HT2C receptor antagonism leads to the opposite effect.Finally, treatment with lithium, tamoxifen, and myricitrin was all found to result in a complete abolishment of the AMPH-induced increase in 50-kHz USV, suggesting the involvement of PKC signaling.

View Article: PubMed Central - PubMed

Affiliation: Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, 35032 Marburg, Germany. markus.woehr@staff.uni-marburg.de.

ABSTRACT
Rats emit high-frequency 50-kHz ultrasonic vocalizations (USV) in appetitive situations like social interactions. Drugs of abuse are probably the most potent non-social elicitors of 50-kHz USV, possibly reflecting their euphorigenic properties. Psychostimulants induce the strongest elevation in 50-kHz USV emission, particularly amphetamine (AMPH), either when applied systemically or locally into the nucleus accumbens (Nacc). Emission of AMPH-induced 50-kHz USV depends on test context, such as the presence of conspecifics, and can be manipulated pharmacologically by targeting major neurotransmitter systems, including dopamine (DA), noradrenaline (NA), and serotonin (5-HT), but also protein kinase C (PKC) signaling. Several D1 and D2 receptor antagonists, as well as typical and atypical antipsychotics block the AMPH-induced elevation in 50-kHz USV. Inhibiting D1 and D2 receptors in the Nacc abolishes AMPH-induced 50-kHz USV, indicating a key role for this brain area. NA neurotransmission also regulates AMPH-induced 50-kHz USV emission given that α 1 receptor antagonists and α 2 receptor agonists exert attenuating effects. Supporting the involvement of the 5-HT system, AMPH-induced 50-kHz USV are attenuated by 5-HT2C receptor activation, whereas 5-HT2C receptor antagonism leads to the opposite effect. Finally, treatment with lithium, tamoxifen, and myricitrin was all found to result in a complete abolishment of the AMPH-induced increase in 50-kHz USV, suggesting the involvement of PKC signaling. Neurotransmitter systems involved in AMPH-induced 50-kHz USV emission only partially overlap with other AMPH-induced behaviors like hyperlocomotion. The validity of AMPHinduced 50-kHz USV as a preclinical model for neuropsychiatric disorders is discussed, particularly with relevance to altered drive and mood seen in bipolar disorder.

No MeSH data available.


Related in: MedlinePlus

Exemplary spectrograms of flat (FLAT; A) and frequency-modulated (FM; B-D) 50-kHz ultrasonic vocalizations (USV), with thelatter consisting of 50-kHz USV characterized by one or more steps/jumps in frequency, so called frequency step calls (B), trills, i.e. zigzagshapedcalls (C), and mixed calls (D).
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Figure 1: Exemplary spectrograms of flat (FLAT; A) and frequency-modulated (FM; B-D) 50-kHz ultrasonic vocalizations (USV), with thelatter consisting of 50-kHz USV characterized by one or more steps/jumps in frequency, so called frequency step calls (B), trills, i.e. zigzagshapedcalls (C), and mixed calls (D).

Mentions: Rats emit different types of vocalizations in the ultrasonic range, commonly referred to as ultrasonic vocalizations (USV; for review see: [1,2]). In juvenile and adult rats, typically two main USV types are differentiated depending on emission context and acoustic features, such as call duration and frequency. Low-frequency USV characterized by long call durations, so called 22-kHz USV, occur in aversive situations and probably reflect a negative emotional state akin anxiety and fear (for review see: [3]). In contrast, high-frequency USV with short call durations, taken together as 50-kHz USV, are emitted in appetitive situations. Under natural conditions, particularly high rates of 50-kHz USV occur during positively reinforcing social interactions, like juveniles rough-and-tumble play (e.g. [4]) and mating in adults (e.g. [5]). Playback studies indicate that 50-kHz USV serve an important communicative function as social contact calls which can maintain or reestablish social proximity by eliciting approach behavior in the recipient (for review see: [6]). Because 50-kHz USV occur almost exclusively in situations that are positively reinforcing, it was repeatedly suggested that 50-kHz USV might reflect a positive emotional state (e.g. [7]). However, it has to be noted that 50-kHz USV are highly complex and characterized by a huge level of variability. In fact, depending on their shape various subtypes can be discriminated. Typically, the different 50-kHz USV subtypes are clustered into flat (FLAT) and frequency-modulated (FM) calls, with the latter consisting of 50-kHz USV characterized by one or more steps/jumps in frequency, so called frequency step calls, trills, i.e. zigzag-shaped calls, and mixed calls (Fig. 1; e.g. [8-16]), yet more complex classification systems with up to 14 subtypes have also been applied (e.g. [17-21]). While FLAT 50-kHz USV may primarily serve a social coordinating function (e.g. [22,23]), it was suggested that FM 50-kHz USV may in particular or even exclusively reflect a positive affective state (e.g. [24,25]). It is in line with this view that drugs with abuse potential are likely the most potent non-social elicitors of 50-kHz USV, particularly of the FM subtype, possibly reflecting the euphorigenic properties of drugs of abuse.


Environmental and Pharmacological Modulation of Amphetamine- Induced 50-kHz Ultrasonic Vocalizations in Rats.

Rippberger H, van Gaalen MM, Schwarting RK, Wohr M - Curr Neuropharmacol (2015)

Exemplary spectrograms of flat (FLAT; A) and frequency-modulated (FM; B-D) 50-kHz ultrasonic vocalizations (USV), with thelatter consisting of 50-kHz USV characterized by one or more steps/jumps in frequency, so called frequency step calls (B), trills, i.e. zigzagshapedcalls (C), and mixed calls (D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4598433&req=5

Figure 1: Exemplary spectrograms of flat (FLAT; A) and frequency-modulated (FM; B-D) 50-kHz ultrasonic vocalizations (USV), with thelatter consisting of 50-kHz USV characterized by one or more steps/jumps in frequency, so called frequency step calls (B), trills, i.e. zigzagshapedcalls (C), and mixed calls (D).
Mentions: Rats emit different types of vocalizations in the ultrasonic range, commonly referred to as ultrasonic vocalizations (USV; for review see: [1,2]). In juvenile and adult rats, typically two main USV types are differentiated depending on emission context and acoustic features, such as call duration and frequency. Low-frequency USV characterized by long call durations, so called 22-kHz USV, occur in aversive situations and probably reflect a negative emotional state akin anxiety and fear (for review see: [3]). In contrast, high-frequency USV with short call durations, taken together as 50-kHz USV, are emitted in appetitive situations. Under natural conditions, particularly high rates of 50-kHz USV occur during positively reinforcing social interactions, like juveniles rough-and-tumble play (e.g. [4]) and mating in adults (e.g. [5]). Playback studies indicate that 50-kHz USV serve an important communicative function as social contact calls which can maintain or reestablish social proximity by eliciting approach behavior in the recipient (for review see: [6]). Because 50-kHz USV occur almost exclusively in situations that are positively reinforcing, it was repeatedly suggested that 50-kHz USV might reflect a positive emotional state (e.g. [7]). However, it has to be noted that 50-kHz USV are highly complex and characterized by a huge level of variability. In fact, depending on their shape various subtypes can be discriminated. Typically, the different 50-kHz USV subtypes are clustered into flat (FLAT) and frequency-modulated (FM) calls, with the latter consisting of 50-kHz USV characterized by one or more steps/jumps in frequency, so called frequency step calls, trills, i.e. zigzag-shaped calls, and mixed calls (Fig. 1; e.g. [8-16]), yet more complex classification systems with up to 14 subtypes have also been applied (e.g. [17-21]). While FLAT 50-kHz USV may primarily serve a social coordinating function (e.g. [22,23]), it was suggested that FM 50-kHz USV may in particular or even exclusively reflect a positive affective state (e.g. [24,25]). It is in line with this view that drugs with abuse potential are likely the most potent non-social elicitors of 50-kHz USV, particularly of the FM subtype, possibly reflecting the euphorigenic properties of drugs of abuse.

Bottom Line: NA neurotransmission also regulates AMPH-induced 50-kHz USV emission given that α 1 receptor antagonists and α 2 receptor agonists exert attenuating effects.Supporting the involvement of the 5-HT system, AMPH-induced 50-kHz USV are attenuated by 5-HT2C receptor activation, whereas 5-HT2C receptor antagonism leads to the opposite effect.Finally, treatment with lithium, tamoxifen, and myricitrin was all found to result in a complete abolishment of the AMPH-induced increase in 50-kHz USV, suggesting the involvement of PKC signaling.

View Article: PubMed Central - PubMed

Affiliation: Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, 35032 Marburg, Germany. markus.woehr@staff.uni-marburg.de.

ABSTRACT
Rats emit high-frequency 50-kHz ultrasonic vocalizations (USV) in appetitive situations like social interactions. Drugs of abuse are probably the most potent non-social elicitors of 50-kHz USV, possibly reflecting their euphorigenic properties. Psychostimulants induce the strongest elevation in 50-kHz USV emission, particularly amphetamine (AMPH), either when applied systemically or locally into the nucleus accumbens (Nacc). Emission of AMPH-induced 50-kHz USV depends on test context, such as the presence of conspecifics, and can be manipulated pharmacologically by targeting major neurotransmitter systems, including dopamine (DA), noradrenaline (NA), and serotonin (5-HT), but also protein kinase C (PKC) signaling. Several D1 and D2 receptor antagonists, as well as typical and atypical antipsychotics block the AMPH-induced elevation in 50-kHz USV. Inhibiting D1 and D2 receptors in the Nacc abolishes AMPH-induced 50-kHz USV, indicating a key role for this brain area. NA neurotransmission also regulates AMPH-induced 50-kHz USV emission given that α 1 receptor antagonists and α 2 receptor agonists exert attenuating effects. Supporting the involvement of the 5-HT system, AMPH-induced 50-kHz USV are attenuated by 5-HT2C receptor activation, whereas 5-HT2C receptor antagonism leads to the opposite effect. Finally, treatment with lithium, tamoxifen, and myricitrin was all found to result in a complete abolishment of the AMPH-induced increase in 50-kHz USV, suggesting the involvement of PKC signaling. Neurotransmitter systems involved in AMPH-induced 50-kHz USV emission only partially overlap with other AMPH-induced behaviors like hyperlocomotion. The validity of AMPHinduced 50-kHz USV as a preclinical model for neuropsychiatric disorders is discussed, particularly with relevance to altered drive and mood seen in bipolar disorder.

No MeSH data available.


Related in: MedlinePlus