Alzheimers disease and cognition

On the basis of anatomical data, studies of CCK on memory processes have constituted an important field of investigation, as this neuropeptide is present in regions such as limbic structure and cortical areas, which are implicated in the control of cognitive processes, motivational and emotional behaviours. It has been suggested that CCK1 and CCK2 receptors have different roles in learning and memory functions (Harro and Oreland 1993). In particular, a balance between CCK1 receptor mediated facilitatory effects and CCK2 receptor mediated inhibitory effects on memory retention has been postulated (Lemaire etal. 1992). However, there are conflicting reports on the effects of CCK2 receptor agonists in animal models of memory. For instance, although some groups have reported that selective CCK2 receptor agonists (CCK4, BC264) impair memory (Lemaire etal. 1992 ; Derrien etal. 1994b), others have found that these peptides enhance memory (Gerhardt et al. 1994). Treatment

BC 264


Fig. 14.2 Effects of i.p. injection of BDNL and BC 264 administered 30 min before the experiment in the elevated plus maze. The behavioural responses of rats were measured in the elevated plus-maze for 5 min and are expressed as the percentage of time spent in open arms. * p < 0.05 and ** p < 0.01 as compared to control group.

with BC264 has also been described to elicit prominent hypervigilance in monkeys and to increase behavioural arousal in rats (review in Dauge and Roques 1995). The latter findings suggest a possible role for CCK2 receptor in attentional activation that can facilitate learning. The apparent discrepancies observed with CCK agonists indicate that CCK2 receptors could have different functions involving alternate neuronal pathways, according to the task carried out by the animal. To date only few studies have been devoted to the effects of CCK receptor agonists on human memory. Recently, Shlik et al. (1998) found that the continuous administration of the selective CCK2 receptor agonists, CCK4, had no effect on psychomotor performance, although it produced impairment in cognitive tests of free recall and recognition. The results of this study suggest that CCK4 may exert a negative influence on memory consolidation and retrieval.

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