Differential effects of ondansetron and α-flupenthixol on responding for conditioned reward (original) (raw)

Abstract

Previous experiments have suggested that 5-HT3 antagonists such as ondansetron may alter reward-related behaviour that is dependent in part upon raised mesolimbic dopamine activity. However, the evidence for this is far from conclusive. One major behavioural role of dopamine is in the control of behaviour elicited by conditioned rewarding stimuli. To date, the effects of 5-HT3 antagonists on this function of mesolimbic dopamine have not been examined. Two experimental procedures were employed to examine the effects of ondansetron (10 and 100 μg/kg) on the acquisition of responding for conditioned reward, and on the response potentiating effect of intra-accumbens _d_-amphetamine (10 μg). These effects were compared to those elicited by the dopamine antagonist α-flupenthixol (0.1 mg/kg). In the first procedure, rats were trained 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 delivering the CS, indicating that this CS functioned as a conditioned reward (CR). Ondansetron administered during the conditioning phase did not alter subsequent responding for the CR, but α-flupenthixol induced 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 relationships. In the second procedure, _d_-amphetamine injected into the nucleus accumbens markedly potentiated responding for CR. Ondansetron at 10 μg/kg induced a small attenuation of this effect, without altering responding in its own right. However, at a higher dose (100 μg/kg) ondansetron plus amphetamine treatment significantly enhanced responding on the inactive lever. At both doses, the net effect of ondansetron was to produce a subtle impairment in the allocation of responses such that the differential responding on the CR versus NCR lever was diminished. In contrast to these effects α-flupenthixol significantly attenuated _d_-amphetamine’s selective enhancement of responding for conditioned reward, as well as impairing the ability of the conditioned reward to elicit and maintain behaviour. These results confirm the role of dopamine in responding for conditioned reward, and suggest a possible modulators role for 5-HT3 receptors in this process. However, the effects of ondansetron on the acquisition of, and responding for, conditioned reward are clearly different from those induced by blockade of dopamine receptors.

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Authors and Affiliations

  1. Section of Biopsychology, Clarke Institute of Psychiatry, Toronto, Ontario, Canada M5T 1R8 Fax +1(416)979-6889, e-mail: fletcher@psych.utoronto.ca, , , , , , CA
    P. J. Fletcher
  2. Neuroscience Unit, GlaxoWellcome Research and Development Ltd, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK, , , , , , GB
    Guy A. Higgins

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  1. P. J. Fletcher
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  2. Guy A. Higgins
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Received:4 December 1996/Final version:30 April 1997

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Fletcher, P., Higgins, G. Differential effects of ondansetron and α-flupenthixol on responding for conditioned reward.Psychopharmacology 134, 64–72 (1997). https://doi.org/10.1007/s002130050426

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