Reassessment of amphetamine- and phencyclidine-induced locomotor hyperactivity as a model of psychosis-like behavior in rats
journal contributionposted on 2022-05-20, 05:47 authored by S Kusljic, Maarten van den BuuseMaarten van den Buuse, A Gogos
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. Pretreatment 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. Hyper-locomotion 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.
This research was part-funded by the National Health and Medical Research Council of Australia (AG CDF 1108098, Project Grant 509234). The Florey Institute of Neuroscience and Mental Health acknowledges the funding from the Victorian Government's Operational Infrastructure Support.
JournalJournal of Integrative Neuroscience
Rights Statement©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/).
Science & TechnologyLife Sciences & BiomedicineNeurosciencesNeurosciences & NeurologyAmphetaminePhencyclidineDopamineNoradrenalineSerotoninPsychosisNUCLEUS-ACCUMBENSALPHA-1-ADRENERGIC RECEPTORSPREFRONTAL CORTEXDOPAMINE RELEASEMK-801NOREPINEPHRINESTIMULATIONHALOPERIDOLINHIBITIONSEROTONINAdrenergic alpha-1 Receptor AntagonistsAkathisia, Drug-InducedAnimalsBehavior, AnimalCentral Nervous System StimulantsDisease Models, AnimalDopamine AntagonistsExcitatory Amino Acid AntagonistsMalePsychoses, Substance-InducedRatsRats, Sprague-DawleySerotonin AntagonistsNeurology & Neurosurgery