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Eur Neuropsychopharmacol. 2016 Dec;26(12):1900-1908. doi: 10.1016/j.euroneuro.2016.10.012. Epub 2016 Nov 12.

Evaluation of 50-kHz ultrasonic vocalizations in animal models of mania: Ketamine and lisdexamfetamine-induced hyperlocomotion in rats.

Author information

1
Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, 81540-990 Curitiba, PR, Brazil.
2
Behavioural Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, 35032 Marburg, Germany.
3
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.

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.

KEYWORDS:

Bipolar disorder; Dopamine; Lithium; Manic; N-methyl-D-aspartate receptor; Positive affect

PMID:
27842942
DOI:
10.1016/j.euroneuro.2016.10.012
[Indexed for MEDLINE]

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