Rapid visual learning in the rat: Effects at the 5-HT1a receptor subtype

Abstract

The 5-hydroxytryptamine1a (5-HT1a) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 0.15 mg/kg) impaired rats' rapid visual learning on a computerized maze. This treatment also increased decision time (DT) but the learning impairment was not necessarily a side-effect of slower responding because, in this task, responses made at long DT are more accurate than those at short DT. The selective 5-HT1a receptor antagonist WAY-100635 (0.3 mg/kg) was itself without effect on accuracy, but was effective in reversing effects of 8-OH-DPAT (on both accuracy and DT). Within problems (i.e., over the 40-60 trials of a single discrimination), performance was reduced by treatment with 8-OH-DPAT at all stages of learning. We conclude that this effect is mediated through the 5-HT1a receptor site (rather than through some other serotonergic receptor site or non-specific mechanism) as it was reversible by treatment with WAY-100635. Although it could still arise from behaviourally non-specific effects, the performance deficit finds its best account in terms of the psychological processes necessary to visual learning. Its reversal with WAY-100635 offers support to the hypothesis that 5-HT1a receptor antagonists could improve cognitive function, under conditions of pre-existing impairment due to overactive serotonergic inhibition, as is thought to occur in Alzheimer's disease.

Role of Hippocampal CaMKII in Serotonin 5-HT1A Receptor-Mediated Learning Deficit in Rats

“…The results suggest that the 5-HT 1A receptormediated disruption of retention performance is a consequence, at least in part, of the reduced phosphorylating activity of CaMKII, a critical mediator of neuronal plasticity and memory. The impaired retention found after administration of a low dose of 8-OH-DPAT, 0.1 mg/kg, is in keeping with many previous data demonstrating deficits not only in passive avoidance Misane et al, 1998;Otano et al, 1999;Santucci and Shaw, 2003) but also in other cognitive tasks such as spatial learning in a water-maze or visual learning in a Y-maze Kant et al, 1998;Cassaday et al, 2000). Previous studies from other laboratories (Misane and Ö gren, 2000), as well as our previous experiments (Otano et al, 1999), had shown that nonspecific effects, such as changes in locomotor activity or in pain threshold, did not account for the 8-OH-DPATinduced impairment in retention performance.…”

Perirhinal cortex ablation in rats selectively impairs object identification in a simultaneous visual comparison task.

“…The evidence of visual encoding of object properties, from electrophysiological and also c-fos activation studies, in the rat temporal cortex (Wan et al, 1999; Zhu et al, 1995) was obtained from this strain. Another pigmented strain, the Hooded Lister, can master the constant-negative task with multi-featured scenes of the kind used for pretraining here, but performs worse than Dark Agoutis (Cassaday, Simpson, & Gaffan, 1999) and we have not tried to train them with the more demanding scenes used in Experiment 1. It remains to be seen whether the visual object identification ability of Dark Agoutis, and its dependence on the PeRh cortex, can be replicated in other strains of rat.…”

Configural learning without configural training.

“…The group mean number of sessions to reach criterion (excluding the two criterial sessions) was 1.7 sessions per problem for the first four single-constant problems with scene stimuli and 0.9 for the next four problems with large-object stimuli. Such rapid learning is typical for this paradigm when a highly discriminable class of stimuli is used (Cassaday, Simpson, & Gaffan, 2000; Gaffan & Woolmore, 1996). The mean number of sessions taken overall to reach criterion on the final pretraining problem with large objects, which had four intermingled constants in its final stage, was 29.8.…”