title: Evaluation of 50-kHz ultrasonic vocalizations in animal models of mania: Ketamine and lisdexamfetamine-induced hyperlocomotion in rats.
abstract: Drug-induced hyperlocomotion in rodents is frequently used as a behavioral model for mania. However, the use of locomotor activity as the single parameter in these animal models of mania may pose some limitations for developing new pharmacological treatments. Thus, alternative behavioral markers are required. Fifty-kHz ultrasonic vocalizations (USV), which are thought to represent positive affect, are increased by the administration of the psychostimulant d-amphetamine, an effect that can be prevented by lithium treatment, the gold standard antimanic drug for treating bipolar disorder. The aim of this study was to evaluate 50-kHz USV in two other pharmacological-induced animal models of mania: ketamine (KET)- and lisdexamfetamine (LDX)-induced hyperlocomotion. After systemic injection of LDX (10mg/kg, ip), racemic-ketamine (25mg/kg, ip) or S-ketamine (25mg/kg, ip), locomotor activity and 50-kHz USV emission were evaluated in rats. Furthermore, the effects of an antimanic treatment, namely lithium carbonate (100mg/kg, ip), on LDX-induced 50-kHz USV and hyperlocomotion were tested. Rats treated with racemic KET and S-KET showed increased locomotor activity, but these drug treatments did not significantly affect 50-kHz USV emission rates. On the other hand, LDX administration increased both locomotor activity and 50-kHz USV with both effects being reversed by lithium administration. The present findings suggest that 50-kHz USV can differentiate between drug-induced models of mania, which may represent different types of manic episodes. Thus, measuring 50-kHz USV might serve as an additional valuable behavioral variable to assess mania-like phenotypes in rat models.
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, 81540-990 Curitiba, PR, Brazil.
authors.forename: Etieli
authors.initials: E
authors.lastname: Wendler
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, 81540-990 Curitiba, PR, Brazil.
authors.forename: Camila Pasquini
authors.initials: CP
authors.lastname: de Souza
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, 81540-990 Curitiba, PR, Brazil.
authors.forename: Debora Dalla
authors.initials: DD
authors.lastname: Vecchia
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, 81540-990 Curitiba, PR, Brazil.
authors.forename: Luiz Kae Sales
authors.initials: LKS
authors.lastname: Kanazawa
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, 81540-990 Curitiba, PR, Brazil.
authors.forename: Palloma
authors.initials: P
authors.lastname: de Almeida Soares Hocayen
authors.affiliation: Behavioural Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, 35032 Marburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Wöhr
authors.affiliation: Behavioural Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, 35032 Marburg, Germany.
authors.forename: Rainer K W
authors.initials: RKW
authors.lastname: Schwarting
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, 81540-990 Curitiba, PR, Brazil. Electronic address: randreatini@ufpr.br.
authors.forename: Roberto
authors.initials: R
authors.lastname: Andreatini
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D007649:Ketamine / Q000494:pharmacology*; D000069478:Lisdexamfetamine Dimesylate / Q000494:pharmacology*; D016651:Lithium Carbonate / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D016651:Lithium Carbonate; D007649:Ketamine; D000069478:Lisdexamfetamine Dimesylate
keywords: Bipolar disorder; Dopamine; Lithium; Manic; N-methyl-D-aspartate receptor; Positive affect