Selective effects of 5-HT2C receptor modulation on performance of a novel valence-probe visual discrimination task and probabilistic reversal learning in mice.
Psychopharmacology (Berl)
; 235(7): 2101-2111, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29682701
ABSTRACT
RATIONALE Dysregulation of the serotonin (5-HT) system is a pathophysiological component in major depressive disorder (MDD), a condition closely associated with abnormal emotional responsivity to positive and negative feedback. However, the precise mechanism through which 5-HT tone biases feedback responsivity remains unclear. 5-HT2C receptors (5-HT2CRs) are closely linked with aspects of depressive symptomatology, including abnormalities in reinforcement processes and response to stress. Thus, we aimed to determine the impact of 5-HT2CR function on response to feedback in biased reinforcement learning. METHODS:
We used two touchscreen assays designed to assess the impact of positive and negative feedback on probabilistic reinforcement in mice, including a novel valence-probe visual discrimination (VPVD) and a probabilistic reversal learning procedure (PRL). Systemic administration of a 5-HT2CR agonist and antagonist resulted in selective changes in the balance of feedback sensitivity bias on these tasks.RESULTS:
Specifically, on VPVD, SB 242084, the 5-HT2CR antagonist, impaired acquisition of a discrimination dependent on appropriate integration of positive and negative feedback. On PRL, SB 242084 at 1 mg/kg resulted in changes in behaviour consistent with reduced sensitivity to positive feedback. In contrast, WAY 163909, the 5-HT2CR agonist, resulted in changes associated with increased sensitivity to positive feedback and decreased sensitivity to negative feedback.CONCLUSIONS:
These results suggest that 5-HT2CRs tightly regulate feedback sensitivity bias in mice with consequent effects on learning and cognitive flexibility and specify a framework for the influence of 5-HT2CRs on sensitivity to reinforcement.Palavras-chave
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MEDLINE
Assunto principal:
Reversão de Aprendizagem
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Azepinas
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Receptor 5-HT2C de Serotonina
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Agonistas do Receptor 5-HT2 de Serotonina
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Antagonistas do Receptor 5-HT2 de Serotonina
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Aminopiridinas
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Indóis
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article