Towards an Understanding of Cognitive Flexibility: Are Hallucinations Necessary for the Enduring Pro-Cognitive Effects of Psychedelics?

Abstract

Abstract: Cognitive flexibility is critical for health psychological functioning and an important transdiagnostic target. Its deficits are prevalent in many psychiatric disorders, yet it is assumed to be intact for efficacy of cognitive-behavioural therapies. Pharmacological adjuncts to psychotherapy would be greatly beneficial for individuals of these disorders. Psychedelics are suggested to improve cognitive flexibility through structural neuroplastic growth induced by partial and full 5-HT2A receptor agonism. But they are also suggested to improve disorder symptoms through their hallucinogenic properties induced only by full 5-HT2A agonism. Therefore, to resolve these competing explanations, a cognitive flexibility animal model will be used. In a probabilistic reversal learning task, female rats were administered with either psilocybin (full agonist), 6-f-det (partial agonist), or saline as control. Therefore, the aim of this experiment is to investigate whether a partial 5-HT2A agonist (6-f-det) can recapitulate the enduring pro-cognitive effects of a full 5-HT2A agonist (psilocybin). It was hypothesised that (1) accuracy, a measure of reversal learning performance, would be significantly higher in psilocybin and 6-f-det administered rats compared to saline control, and (2) psilocybin will produce higher accuracy scores than 6-f-det, likely to due to the different magnitude of effects for full vs partial 5-HT2A agonism. See 'pre-registration form' under 'files' for detailed background and methods.

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