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Global 5-HT depletion improves serial spatial reversal learning in the rat
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2013 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Global 5-HT depletion improves serial spatial reversal learning in the rat

Laura Nilsson Suonvieri

Supervisor: Johan Alsiö, Department of Psychology, University of Cambridge

Examiner: Erika Roman, Department of Pharmaceutical Biosciences, Uppsala University



BACKGROUND: Behavioural inflexibility, the inability to adapt to environmental changes, is a key deficit in many psychiatric disorders such as schizophrenia and obsessive-compulsive disorder (OCD). Unfortunately, no current drugs efficiently address this deficit. Behavioural flexibility is often assessed using reversal learning tasks. Previous research suggests that reversal learning is dependent on the orbitofrontal cortex (OFC) and may be modulated by serotonin (5-HT). AIM: This study aimed to further characterize the neural circuits underlying reversal learning by investigating the effects of global and selective OFC 5-HT depletion on rats’ performance on a serial spatial reversal learning task. METHODS: Rats were initially trained to respond at only one of two lit nose-poke holes (e.g. left but not right). Prior to reversal, rats received either intracerebroventicular (global depletion/sham) or intra-OFC (OFC depletion/sham) infusions of either 5,7-DHT (a serotonergic neurotoxin causing a permanent depletion of 5-HT) or vehicle alone. This was followed by a series of reversals where the reward contingencies changed (e.g. right was correct instead of left). RESULTS: Global 5-HT depletion improved reversal learning by reducing the number of errors made. It also improved the retention of the reversals but did not affect the retention of preoperatively learned discrimination or the acquisition of a novel discrimination. OFC 5-HT depletion did not significantly affect any of the behavioural measures. CONCLUSION: In contrast to previous studies, our results show that global 5-HT depletion improves reversal learning whereas OFC depleted rats seem unaffected. Since no effect was seen of OFC 5-HT depletion, further studies are needed to investigate the possible brain region responsible for the facilitating effects of global 5-HT depletion on serial spatial reversal learning in rats.

Place, publisher, year, edition, pages
2013. , 34 p.
Keyword [en]
Reversal learning, cognitive flexibility, behavioural flexibility, schizophrenia, 5-HT depletion
National Category
Neurosciences Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-203126OAI: oai:DiVA.org:uu-203126DiVA: diva2:635132
External cooperation
Department of Psychology, University of Cambridge
Educational program
Master of Science Programme in Pharmacy
Available from: 2013-07-04 Created: 2013-07-02 Last updated: 2013-07-04Bibliographically approved

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