14 research outputs found

    Post-training depletions of basolateral amygdala serotonin fail to disrupt discrimination, retention, or reversal learning.

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    In goal-directed pursuits, the basolateral amygdala (BLA) is critical in learning about changes in the value of rewards. BLA-lesioned rats show enhanced reversal learning, a task employed to measure the flexibility of response to changes in reward. Similarly, there is a trend for enhanced discrimination learning, suggesting that BLA may modulate formation of stimulus-reward associations. There is a parallel literature on the importance of serotonin (5HT) in new stimulus-reward and reversal learning. Recent postulations implicate 5HT in learning from punishment. Whereas, dopaminergic involvement is critical in behavioral activation and reinforcement, 5HT may be most critical for aversive processing and behavioral inhibition, complementary cognitive processes. Given these findings, a 5HT-mediated mechanism in BLA may mediate the facilitated learning observed previously. The present study investigated the effects of selective 5HT lesions in BLA using 5,7-dihydroxytryptamine (5,7-DHT) vs. infusions of saline (Sham) on discrimination, retention, and deterministic reversal learning. Rats were required to reach an 85% correct pairwise discrimination and single reversal criterion prior to surgery. Postoperatively, rats were then tested on the (1) retention of the pretreatment discrimination pair, (2) discrimination of a novel pair, and (3) reversal learning performance. We found statistically comparable preoperative learning rates between groups, intact postoperative retention, and unaltered novel discrimination and reversal learning in 5,7-DHT rats. These findings suggest that 5HT in BLA is not required for formation and flexible adjustment of new stimulus-reward associations when the strategy to efficiently solve the task has already been learned. Given the complementary role of orbitofrontal cortex in reward learning and its interconnectivity with BLA, these findings add to the list of dissociable mechanisms for BLA and orbitofrontal cortex in reward learning

    The role of 5-HT2C receptors in touchscreen visual reversal learning in the rat: a cross-site study.

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    RATIONALE: Reversal learning requires associative learning and executive functioning to suppress non-adaptive responding. Reversal-learning deficits are observed in e.g. schizophrenia and obsessive-compulsive disorder and implicate neural circuitry including the orbitofrontal cortex (OFC). Serotonergic function has been strongly linked to visual reversal learning in humans and experimental animals but less is known about which receptor subtypes are involved. OBJECTIVES: The objectives of the study were to test the effects of systemic and intra-OFC 5-HT2C-receptor antagonism on visual reversal learning in rats and assess the psychological mechanisms underlying these effects within novel touchscreen paradigms. METHODS: In experiments 1-2, we used a novel 3-stimulus task to investigate the effects of 5-HT2C-receptor antagonism through SB 242084 (0.1, 0.5 and 1.0 mg/kg i.p.) cross-site. Experiment 3 assessed the effects of SB 242084 in 2-choice reversal learning. In experiment 4, we validated a novel touchscreen serial visual reversal task suitable for neuropharmacological microinfusions by baclofen-/muscimol-induced OFC inactivation. In experiment 5, we tested the effect of intra-OFC SB 242084 (1.0 or 3.0 μg/side) on performance in this task. RESULTS: In experiments 1-3, SB 242084 reduced early errors but increased late errors to criterion. In experiment 5, intra-OFC SB 242084 reduced early errors without increasing late errors in a reversal paradigm validated as OFC dependent (experiment 4). CONCLUSION: Intra-OFC 5-HT2C-receptor antagonism decreases perseveration in novel touchscreen reversal-learning paradigms for the rat. Systemic 5-HT2C-receptor antagonism additionally impairs late learning-a robust effect observed cross-site and potentially linked to impulsivity. These conclusions are discussed in terms of neural mechanisms underlying reversal learning and their relevance to psychiatric disorders.The research leading to these results has received support from the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The study was also supported by a Wellcome Trust Grant (089589/z/09/z) to T.W.R., B.J. Everitt, B.J. Sahakian, A.C. Roberts and J.W. Dalley, and by a Wellcome Trust Senior Investigator Award to T.W.R. (104631/Z/14/Z). The Behavioural and Clinical Neuroscience Institute is co-funded by the Medical Research Council and the Wellcome Trust. J.A. was supported by the Swedish Pharmaceutical Society and the Swedish Research Council (350-2012-230). S.R.O.N was supported by BBSRC and Eli Lilly through CASE studentship (BB/F529054/1).This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00213-015-3963-

    The neuropsychopharmacology of reversal learning

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    Reversal learning deficits are a feature of many neuropsychiatric disorders, most notably schizophrenia. These deficits could be due, in part, to altered ability to dissipate either or both associations of previous positive (perseverance) and negative (learned non-reward) valence. Studies reported in this thesis developed an egocentric maze task and a visuospatial operant task for separate assessments of spatial reversal learning, perseverance and learned non-reward in mice. These tasks were subsequently used to assess the cognitive causes for altered performance after manipulations to brain systems recognised to be involved in reversal learning and relevant for human psychopathology, with a specific focus on schizophrenia. NMDA receptor (NMDAr) antagonism through acute phencyclidine did not affect reversal learning in the operant task, but caused general impairments in the maze task. Orbitofrontal (OFC) lesioned mice showed perseverative impairments in the operant task. Mice treated with the 5-HT2C receptor (5-HT2CR) antagonist SB242084 and 5-HT2CR KO mice showed facilitated reversal learning and decreased learned nonreward in the operant task. In the maze task, SB242084 decreased perseverance but increased learned non-reward, while 5-HT2CR KO mice showed perseverance and discrimination learning deficits. The final experimental chapter investigated the effect of SB242084 on touch-screen visual reversal learning in the rat. SB242084 retarded learning in this task. These studies demonstrate that previously non-reinforced associations can be of considerable importance in tasks of cognitive flexibility. The studies also show that the NMDAr, the 5-HT2CR, and the OFC, are involved in reversal learning and can modulate mechanisms related to both perseverance and learned non-reward. Moreover, in reversal learning, few effects of manipulations affecting PFC-functioning, or activity at the NMDAr and 5-HT2CR, generalise across the procedures in the visuospatial, egocentric spatial, and visual domains

    Inhibition of prandial and waterspray-induced rat grooming by 8-OH-DPAT

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    The effects of 8-OH-DPAT treatment on rat grooming behaviour, elicited either prandially or in response to spraying with water were investigated. Dose (≤0.1 mg/kg s.c.) response studies employed momentary time sampling over 30 or 60 min with behaviour being scored in one of 6 or 7 (depending on food availability) mutually exclusive categories (feeding, active, scratching, face-grooming, body grooming, genital-grooming and resting) at 15 s intervals. In non-deprived rats, tested with wet mash available, feeding and activity frequencies were increased, but resting and total grooming were inhibited by 8-OH-DPAT. Face-, body- and genital-grooming occurred at higher levels than scratching, but all categories were reduced with reductions in scratching occurring at a lower dose (0.01 mg/kg). Misting rats with a fine water spray selectively increased body grooming and decreased activity without altering feeding, while 8-OH-DPAT increased feeding and reduced face-, body- and genital-grooming, without affecting already low levels of scratching. In misted rats, tested without food, 8-OH-DPAT reduced face-, body- and genital-grooming and increased resting. These results confirm i) that the water spray technique is a useful method for increasing grooming and ii) that 8-OH-DPAT has a suppressant effect on grooming independent of response competition from enhanced feeding
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