Buspirone differentially modifies short-term memory function in a combined delayed matching/non-matching to position task

This study investigated the action of 5-hydroxytryptamine (5-HT) mimetics on short-term memory function. The objective was to determine whether two closely related tasks could differentiate between partial 5-HT_1A receptor activation, full 5-HT_1A receptor activation and generalised enhanced serotonin (5-HT) activity. Male hooded Lister rats were trained to perform an operant-based combined delayed matching/non-matching to position task. Drugs used were: fluoxetine (3 mg/kg, i.p.), a selective 5-HT reuptake inhibitor; the full 5-HT_1A receptor agonist, 8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT; 0.3 mg/kg, s.c.); and the partial 5-HT _1A receptor agonist, buspirone (1 mg/kg, i.p.). Buspirone differentially disrupted response accuracy depending on the style of trial. There was no such difference in the case of 8-OH-DPAT, which impaired accuracy in both delayed matching/non-matching to position task, while fluoxetine affected neither. Thus, the findings suggest that partial 5-HT_1A receptor activation compromises cognitive function to a greater extent than full 5-HT_1A receptor activation, although a dopaminergic component cannot be excluded since buspirone possesses some dopamine D2 receptor antagonist activity. Furthermore, it suggests that there is a differential role for 5-HT in these two closely related behavioural tasks.