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

The 5-hydroxytrgptamine(1a) (5-HT1a) receptor agonist 8-hydroxy-2-(di-n-pro pylamino) tetralin (8-OH-DPAT; 0.15 mg/kg) impaired rats' rapid visual lear ning on a computerized maze. This treatment also increased decision time (D T) but, the learning impairment was nor necessarily a side-effect of slower responding because, in this task, responses made at long DT are more accur ate than those at short DT. The selective 5-HT1a receptor antagonist WAY-10 0635 (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 10-60 trials of a single discrimination), performance was r educed by treatment with 8-OH-DPAT at all stages of learning. We conclude t hat this effect is mediated through the 5-HT1a receptor site (rather than t hrough some other serotonergic receptor site or non-specific mechanism) as it was reversible by treatment with WAY-100635. Although it could still ari se from behaviourally non-specific effects, the performance deficit finds i ts best account in terms of the psychological processes necessary to visual learning. Its reversal with WAY-100635 offers support to the hypothesis th at 5-HT1a receptor antagonists could improve cognitive function, under cond itions of pre-existing impairment due to overactive serotonergic inhibition , as is thought to occur in Alzheimer's disease.