Scopolamine model

Wesnes K, Simpson PM, White L, Pinker S, Jertz G, Murphy M and Siegfried K (1991). Cholinesterase inhibition in the scopolamine model of dementia. Annals of the New York Academy of Sciences, 640, 268-271. 

Ebert U, Kirch W. (1998). Scopolamine model of dementia electroencephalogram findings and cognitive performance. EurJ Clin Investigation. 28(11) 944-49. 

Molchan SE, Martinez RA, Hill JL, Weingartner HJ, Thompson K, Vitiello B, Sunderland T. (1992). Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model. Brain Res Rev. 17(3) 215-26. 

Many, and quite differentiated, drug effects can be shown and quantified in healthy volunteers under standardized and thus reproducible conditions. The information gathered in these experiments can be usefully applied in a number of theoretical and practical contexts. This chapter has not dealt with some of the herbal medicines, and we also omitted discussion of older studies with simultaneous or consecutive administration of more than one drug, e.g. the so-called scopolamine model to study cognition enhancers (see Spiegel, 1989, p. 180). As will be noted in Chapter 5, experiments in healthy volunteers still play their role in the development of new drugs, some of them under the new name of proof of concept (PoC) or proof of effect (PoE) studies. 

Preda, L., Alberoni, M., Bressi, S., et al. Effects of acute doses of oxiracetam in the scopolamine model of human amnesia. Psychopharmacology (Berlin) 110(4), 421-426, 1993. 

Preston, G.C., Brazell, C., Ward, C., Broks, P., Traub, M., and Stahl, S.M. (1988) The scopolamine model of dementia determination of central cholinomimetic effects of phy-sostigmine on cognition and biochemical markers in man. Journal of Psychopharmacology 2(2), 67-79. 

Drug solutions and implantation of osmotic mini-pumps Physostigmine hemisulphate and procyclidine hydrochlorid were obtained from Sigma (St.Louis, U.S.A.), scopolamine hydrobromid from Merck (Darmstadt, Germany), atropine sulphate was obtained from ACF (Amsterdam, The Netherlands), and diazepam from Roche (The Netherlands). HI-6 was made available by the Defence Research Establishment, Suffield, Canada. Soman (O-pinacolyl methylphosphonofluoridate) was synthesised at TNO. Alzet Osmotic Mini-pumps with a constant delivery rate of 0.55 pl/hr (Model 2002, Alza Corp., Palo Alto, USA) were used to deliver PYR, PHY and SCO. The vehicle consisted of 20% propylene glycol, 10% ethanol and 70% water. The pumps were implanted subcutaneously under isoflurane/02 inhalation anesthesia. 

Cognitive enhancing effects of 5-HT3 receptor antagonists have been observed in several animal models, using both normal animals and animals in which a cognitive deficit has been induced by the administration of the muscarinic antagonist scopolamine [41]. An example is the Wisconsin test, in which marmosets learn to discriminate which of two objects conceal a food reward and, after learning this, the task is reversed such that the food is hidden beneath the other object. Treatment with ondansetron has been shown to enhance the ability of marmosets to learn the reversal task. 

Administration of scopolamine to rats induces amnesia in passive avoidance learning. EGb administered intraperitoneally 30 mm before the initial trial at doses of 150-500 mg/kg significantly attenuated the amnesic effects of scopolamine on step-through latencies in a retention trial 4 hours after training for the passive avoidance test in rats [107]. Hoyer et d. showed that, using an animal model of in tracer ebroventricular streptozotocin treatment, EGb treatment compensated for deterioration in working memory, reference memory and passive... 

Curran, H.V., Schifano, F., and Lader, M., Models of memory dysfunction A comparison of the effects of scopolamine and lorazepam on memory, psychomotor performance and mood, Psychopharmacology, 103, 83, 1991. 

Of course, one caveat for all the aforementioned studies is that they were performed in nonimpaired animals. However, R065-7199 improves scopolamine-induced deficits in this task (37) and recent data from Foley et al. (102) showed that chronic treatment with SB-271046 (once daily, 40 d) improved the age-related impairment in spatial learning and memory in 20-mo-old Wistar rats, an effect also seen in aged Fisher 344 rats (103). Further testing of 5-htg receptor antagonists in glutamate-deficiency models and neurodevelopment-deficiency models is suggested. 

Bartus RT, Johnson HR (1976) Short-term memory in the rhesus monkey disruption from the anti-choUnergic scopolamine. Pharmacol Biochem Behav 5 39-46 Bayer TA, Wirths O (2008) Review on the APP/PS1K1 mouse model intraneuronal Abeta accumulation triggers axonopathy, neuron loss and working memory impairment. Genes Brain Behav 7(Suppl 1) 6-11... 

Signal Transduction Model The pharmacological effects of drugs may be mediated by a time-dependent signal transduction process, which involves multiple steps. Sun and Jusko proposed a signal transduction model to account for the delayed effect of pharmacodynamic responses. This model has been used to characterize the parasympathomimetic activity of scopolamine and atropine in rats. ... 

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