Neuropharmacology
January 1, 2011
Maarten Van den Buuse, Emma Ruimschotel, Sally Martin et al.
37 citations
Mice lacking the serotonin-1A (5-HT(1A)) receptor showed enhanced hyperactivity in response to amphetamine, a model of the hyperdopaminergic state linked to psychosis. The response to MK-801, which models NMDA receptor hypoactivity, was unchanged. The effect of the hallucinogen 5-MeO-DMT was markedly reduced in the knockout mice. No changes were seen in sensory gating deficits induced by apomorphine, nor in the density of dopamine transporters or D1/D2 receptors. These results suggest that 5-HT(1A) receptors play a role in hallucinations and modulating dopamine activity, extending insight into their possible involvement in schizophrenia.
Frontiers in Pharmacology
January 1, 2013
Wendy K. Adams, Adam L. Halberstadt, Maarten Van den Buuse
11 citations
Blocking NMDA receptors with phencyclidine (PCP) can produce schizophrenia-like symptoms in humans, but PCP also affects other systems. Rats with serotonin-depleting lesions in the dorsal hippocampus showed increased hyperactivity from PCP but not from the more selective NMDA blocker MK-801. Lesions in the ventral hippocampus had no effect. PCP and MK-801 both made the rats' movement paths smoother and less predictable, but the dorsal hippocampus lesions did not alter these qualitative effects for PCP, though they slightly reduced MK-801's effect on unpredictability. The results reveal a functional difference between PCP and MK-801 related to serotonin in the dorsal hippocampus, relevant to schizophrenia research.
Journal of Integrative Neuroscience
January 28, 2022
Snezana Kusljic, Maarten Van den Buuse, Andrea Gogos
Locomotor hyperactivity triggered by psychotomimetic drugs like amphetamine and phencyclidine is often linked to dopamine and NMDA receptors, but their pharmacological profiles are more complex. In 32 rats, pre-treatment with haloperidol (dopamine antagonist) or prazosin (noradrenaline antagonist) reduced amphetamine-induced hyperactivity, while ritanserin (serotonin antagonist) had only a partial effect. None of these pre-treatments significantly altered phencyclidine-induced hyperactivity. The findings indicate that both noradrenergic and dopaminergic systems are critical for amphetamine's effects, whereas phencyclidine's hyperlocomotion likely depends on NMDA receptor antagonism. This helps interpret drug-induced hyperactivity as a model of psychosis.
Behavioural Brain Research
March 30, 2017
Andrea Gogos, Snezana Kusljic, Shane J Thwaites et al.
Acute amphetamine caused greater distance traveled (locomotor hyperactivity) in female rats than in male rats, while phencyclidine-induced locomotor hyperactivity was similar in both sexes. No sex differences were observed in amphetamine- or phencyclidine-induced disruption of prepulse inhibition. Male rats showed an increased startle response after amphetamine. These findings suggest that sensitivity to amphetamine, but not phencyclidine, differs between male and female rats, and this sex difference is selective to locomotor hyperactivity and startle, not prepulse inhibition.
Behavioural Brain Research
August 22, 2008
Sally Martin, Maarten Van den Buuse
Depleting serotonin in the forebrain of mice, specifically by destroying serotonin neurons projecting from the median raphe nucleus, made the animals hyperactive at baseline and increased their hyperactivity response to phencyclidine, a drug that can induce psychosis-like behaviors. The same lesion did not affect hyperactivity caused by amphetamine or a measure of sensorimotor gating called prepulse inhibition. Serotonin levels dropped by 68% in the hippocampus and 31% in the striatum. These results, consistent with earlier rat studies, suggest that serotonin release in the dorsal hippocampus normally dampens excessive behavioral stimulation. Disruption of this pathway may contribute to psychosis, and enhancing it could be a mechanism for antipsychotic drugs.