Mark S. Duxon

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The neuropeptide orexin-A modulates the sleep-wake cycle such that central administration to rats increases arousal, reduces slow-wave-sleep (SWS) and paradoxical sleep (PS) and delays PS onset. The contribution of orexin-1 and -2 receptor (OXR) activation to this orexin-A response is still unknown. Using the OX(1)R antagonist SB-334867-A we investigated(More)
Rationale: Orexins A and B have recently been discovered and shown to be derived from prepro-orexin, primarily expressed in the rat hypothalamus. Orexin-A has been ascribed a number of in vivo functions in the rat after intracerebroventricular (ICV) administration, including hyperphagia, neuroendocrine modulation and, most recently, evidence for a(More)
5-HT(2) receptor antagonists promote slow wave sleep (SWS) in humans and rats, conversely 5-HT(2) agonists inhibit SWS in rats. These alterations are thought to be predominantly mediated via the 5-HT(2C) receptor subtype. It is evident that 5-HT(2) receptor function also plays an important role in depression. Here, we examine the acute effect of the(More)
We report here the use of rat high-light social interaction to model the temporal anxiolytic/antidepressant effects of SSRIs seen in the clinic. Compared to vehicle controls, 21, but not 14, days of paroxetine treatment (3 mg kg(-1), p.o., daily) produced a marked increase in rat social interaction (Vehicle=71.3+/-7.3 s; Paroxetine=116.7+/-14.7 s; P<0.01)(More)
Neuromedin-U (NmU) is an agonist at NMU1R and NMU2R. The brain distribution of NmU and its receptors, in particular NMU2R, suggests widespread central roles for NmU. In agreement, centrally administered NmU affects feeding behaviour, energy expenditure and pituitary output. Further central nervous system (CNS) roles for NmU warrant investigation. To(More)
Abstract Rationale and objectives. m-Chlorophenylpiperazine (mCPP) induces panic in humans and dose dependently increases unconditioned escape behaviour in a novel pre-clinical model of extreme anxiety in rats, the unstable elevated exposed plus maze (UEEPM). Numerous studies indicate that the anxiogenic effects of mCPP may be mediated by its action at the(More)
A newly developed apparatus for automated behavioural analysis, Laboratory Animal Behaviour Observation, Registration and Analysis System (LABORAS), has been further validated with respect to the ability of the system to detect the pharmacodynamic effects of standard pharmacological tools. Data were obtained from rats administered with mCPP (reversal with(More)
N-(2,5-Dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134) potently inhibited [125I]SB-258585 and [3H]LSD binding in a HeLa cell line expressing human 5-HT(6) receptors (pK(i)=8.6 and 8.54, respectively). Furthermore, SB-357134 inhibited [125I]SB-258585 binding in human caudate--putamen and in rat and pig striatum membranes(More)
Abstract Rationale and objectives. The unstable elevated exposed plus maze (UEEPM) has been proposed as a novel model of anxiety which elicits unconditioned escape-related behaviour in rats thought to mimic the persistent "fight/flight" state exhibited by patients suffering from extreme anxiety disorders. This study investigated the predictive validity of(More)
Preclinical assessment of drug abuse and dependence has been the subject of several recent regulatory guidelines. Both the European and US authorities recommend a tiered approach and are generally aligned on the methods which should be used. The first tier simply compares the pharmacology of the novel substance to known drugs of abuse. The second tier aims(More)