title: Environmental and Pharmacological Modulation of Amphetamine- Induced 50-kHz Ultrasonic Vocalizations in Rats.
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.
authors.forename: Henrike
authors.initials: H
authors.lastname: Rippberger
authors.forename: Marcel M
authors.initials: MM
authors.lastname: van Gaalen
authors.forename: Rainer K W
authors.initials: RK
authors.lastname: Schwarting
authors.affiliation: Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, 35032 Marburg, Germany. markus.woehr@staff.uni-marburg.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Wohr
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004777:Environment; D008845:Microinjections; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D018377:Neurotransmitter Agents; D000661:Amphetamine