Scopolamine-induced cognitive deficits

Liu T, Xia Z, Zhang WW, Xu JR, Ge XX, Li J et al (2013) Bis(9)-(-)-nor-meptazinol as a novel dual-binding AChEI potently ameliorates scopolamine-induced cognitive deficits in mice. Pharmacol Biochem Behav 104 138-143... 

Carey GJ, Costall B, Domeney AM, Gerrard PA, Jones DN, Naylor RJ, Tyers MB (1992) Ondansetron and arecoline prevent scopolamine-induced cognitive deficits in the marmoset. Pharmacol Biochem Behav 42 75-83... 

To reveal the cognition-enhancing potential of the S-HTj antagonists, studies in age-related memory impairment have been carried out with psy-chiatrically healthy subjects impaired with scopolamine and patients with dementia. In a randomized double-blind, double-dummy, four-way crossover study in a small number of subjects, each psychiatrically healthy male subject received placebo, scopolamine [0.4 mg im], scopolamine plus alosetron [10 J,g iv], or alosetron [250 Jg] [Preston 1994 Preston et al. 1991). Assessments of verbal and spatial memory, sedation, and sustained attention were performed before and after treatment. The main results from the study were that scopolamine induced robust deficits on all primary variables measured, the reduction in verbal and spatial memories being attenuated by 10- Jg and 250- Jg doses of alosetron, respectively. No effects on the sedation or on changes in attention were noted. 

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. 

Most other alkaloids shown to have AChE inhibitory activity have been isolated from plants used in traditional medicine. Coptis chinensis Franch has been used in TCM for several conditions including age-related cognitive and memory decHne. Some alkaloids found in this species e.g. berberine (43), coptisine (44) and palmatine (45) are reported to also be antiChE. Coptis chinensis extract improved a scopolamine-induced learning and memory deficit in rats and this is likely to be due to the alkaloids present thus raising ACh levels. Berberine (43) has been shown to selectively inhibit AChE compared with Bu ChE and it has been shown to improve scopolamine-induced amnesia in rats. ... 

On the other hand, 5-HT1A receptor antagonists have been shown to attenuate or reverse the cognitive deficits induced by the cholinergic blocker scopolamine, which might suggest a new therapeutic activity for this drug class (203,204). 

Carvacrol also improves cognitive activity. Azizi et al. [100] examined the effect of carvacrol and thymol in two rat models of dementia deficits caused by amyloid p and by scopolamine. The method they used was the Morris water maze test and they also assessed the acute toxicity of both carvacrol and thymol. The result showed that both substances could reverse and alleviate the induced cognitive impairments, for example, the escape latency and reduction in target quadrant entries. Both substances also were shown to be relative safe, with LD50s of thymol (565.7 mg/kg) and carvacrol (471.2 mg/kg) that were significantly higher than the therapeutic concentration. The authors also suggest that the antioxidative, antiinflammatory, and anti-choUnesterase activity could be involved in these activities. 

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