| Summary: | 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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