DIFFERENTIAL-EFFECTS OF ONDANSETRON AND ALPHA-FLUPENTIXOL ON RESPONDING FOR CONDITIONED REWARD

Previous experiments have suggested that 5-HT3 antagonists such as ond ansetron may alter reward-related behaviour that is dependent in part upon raised mesolimbic dopamine activity. However, the evidence for th is is far from conclusive. One major behavioural role of dopamine is i n the control of behaviour elicited by conditioned rewarding stimuli. To date, the effects of 5-HT3 antagonists on this function of mesolimb ic dopamine have not been examined. Two experimental procedures were e mployed to examine the effects of ondansetron (10 and 100 mu g/kg) on the acquisition of responding for conditioned reward, and on the respo nse potentiating effect of intra-accumbens d-amphetamine (10 mu g). Th ese effects were compared to those elicited by the dopamine antagonist alpha-flupenthixol (0.1 mg/kg). In the first procedure, rats were tra ined to associate food pellet delivery with a conditioned stimulus (CS ). Rats subsequently allowed to respond on a lever delivering this CS, and on an inactive lever, showed a greater preference for the lever d elivering the CS, indicating that this CS functioned as a conditioned reward (CR). Ondansetron administered during the conditioning phase di d not alter subsequent responding for the CR, but alpha-flupenthixol i nduced a small but significant reduction in responding on the CR lever , These results suggest that blockade of dopamine receptors, but not 5 -HT3 receptors interfere with the learning of stimulus reward relation ships. In the second procedure, d-amphetamine injected into the nucleu s accumbens markedly potentiated responding for CR. Ondansetron at 10 mu g/kg induced a small attenuation of this effect, without altering r esponding in its own right, However, at a higher dose (100 mu g/kg) on dansetron plus amphetamine treatment significantly enhanced responding on the inactive lever, At both doses, the net effect of ondansetron w as to produce a subtle impairment in the allocation of responses such that the differential responding on the CR versus NCR lever was dimini shed. In contrast to these effects alpha-flupenthixol significantly at tenuated d-amphetamine's selective enhancement of responding for condi tioned reward, as well as impairing the ability of the conditioned rew ard to elicit and maintain behaviour. These results confirm the role o f dopamine in responding for conditioned reward, and suggest a possibl e modulators role for 5-HT3 receptors in this process, However, the ef fects of ondansetron on the acquisition of, and responding for, condit ioned reward are clearly different from those induced by blockade of d opamine receptors.