Mitchell, Christopher James; (1995) Conditioned side effects of cancer chemotherapy. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The evidence for the occurrence of two side effects of cancer chemotherapy, taste aversions and anticipatory nausea and vomiting (ANV) was reviewed. It was suggested that both taste aversions and ANV occur as a result of classical conditioning. Thus, investigation of possible interventions for the control of these side effects using a rat model was proposed. First, two pharmacological interventions were tested for their efficacy in the attenuation of CTA. The compounds tested were 5-HT3 and NK1 receptor antagonists both of which have been found to have antiemetic properties. Two 5-HT3 receptor antagonists, ondansetron and granisetron, failed to attenuate cisplatin-induced CTA in rats. Two NK1 antagonists, CP-99,994 and L-742,694, were tested against cisplatin in the formation of CTA. High dose L-742,694 partially blocked CTA, probably through blocking the activity of substance P in the nucleus of the solitary tract or the parabrachial nucleus. A previously tested psychological intervention for the control of CTA in cancer patients is the presentation of a novel "scapegoat" flavour before drug infusion, which is thought to overshadow aversions towards normal dietary items. Using a rat model, it was found that the scapegoat flavour, in addition to overshadowing CTA to previously consumed flavours, may potentiate an aversion to the context in which it was presented. However, further experiments suggested that potentiation may not occur if the flavour presented in the context is varied across each trial. Therefore, presentation of different scapegoat flavours on each visit to the clinic may lead to a reduction in CTA with no accompanying increase in the context aversion (ANV). It was concluded that NK1, but not 5-HT3, receptor antagonists may lead to an attenuation of CTA, and possibly ANV, in cancer chemotherapy patients. Further interventions for the control of ANV and CTA based on learning theoretic principles were suggested.

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