Reassessment of amphetamine- and phencyclidine-induced locomotor hyperactivity as a model of psychosis-like behavior in rats

Kusljic, Snezana, van den Buuse, Maarten, and Gogos, Andrea (2022) Reassessment of amphetamine- and phencyclidine-induced locomotor hyperactivity as a model of psychosis-like behavior in rats. Journal of Integrative Neuroscience, 21 (1). 17.

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Abstract

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.

Item ID: 74759
Item Type: Article (Research - C1)
ISSN: 1757-448X
Keywords: Amphetamine, Dopamine, Noradrenaline, Phencyclidine, Psychosis, Serotonin
Copyright Information: © 2022 The Author(s). Published by IMR Press. This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Date Deposited: 01 Dec 2022 23:31
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320221 Psychiatry (incl. psychotherapy) @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320905 Neurology and neuromuscular diseases @ 50%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200199 Clinical health not elsewhere classified @ 100%
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