Locomotor hyperactivity induced by psychotomimetic drugs, such as amphetamine and phencyclidine, is widely used as an animal model of psychosis-like behaviour and is commonly attributed to an interaction with dopamine release and N-methyl-D-aspartate (NMDA) receptors, respectively. However, what is often not sufficiently taken into account is that the pharmacological profile of these drugs is complex and may involve other neurotransmitter/receptor systems. Therefore, this study aimed to assess the effect of three antagonists targeting different monoamine pathways on amphetamine- and phencyclidine-induced locomotor hyperactivity. A total of 32 rats were pre-treated with antagonists affecting dopaminergic, noradrenergic and serotonergic transmission: haloperidol (0.05 mg/kg), prazosin (2 mg/kg) and ritanserin (1 mg/kg), respectively. After 30 min of spontaneous activity, rats were injected with amphetamine (0.5 mg/kg) or phencyclidine (2.5 mg/kg) and distance travelled, stereotypy and rearing recorded in photocell cages over 90 min. Pre-treatment with haloperidol or prazosin both reduced amphetamine-induced hyperactivity although pre-treatment with ritanserin had only a partial effect. None of the pre-treatments significantly altered the hyperlocomotion effects of phencyclidine. These findings suggest that noradrenergic as well as dopaminergic neurotransmission is critical for amphetamine-induced locomotor hyperactivity. Hyperlocomotion effects of phencyclidine are dependent on other factors, most likely NMDA receptor antagonism. These results help to interpret psychotomimetic drug-induced locomotor hyperactivity as an experimental model of psychosis.
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Reassessment of amphetamine- and phencyclidine-induced locomotor hyperactivity as a model of psychosis-like behavior in rats
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1
Behavioral Neuroscience Laboratory, Mental Health Research Institute, 3052 Parkville, Australia
2
Department of Nursing, The University of Melbourne, 3052 Parkville, Australia
3
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 3052 Parkville, Australia
4
School of Psychology and Public Health, La Trobe University, 3086 Melbourne, Australia
5
Department of Pharmacology, The University of Melbourne, 3052 Parkville, Australia
6
The College of Public Health, Medical and Veterinary Sciences, James Cook University, 4811 Townsville, Australia
*Correspondence: skusljic@unimelb.edu.au (Snezana Kusljic)
J. Integr. Neurosci. 2022, 21(1), 17;
https://doi.org/10.31083/j.jin2101017
Submitted: 25 May 2021 | Revised: 13 July 2021 | Accepted: 12 August 2021 | Published: 28 January 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract
Keywords
Amphetamine
Phencyclidine
Dopamine
Noradrenaline
Serotonin
Psychosis
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