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Glutamatergic and serotonergic modulation of rat medial and lateral orbitofrontal cortex in visual serial reversal learning.
Author(s) -
Mona El-Sayed Hervig,
Louise Piilgaard,
Tadej Božič,
Johan Alsiö,
Trevor W. Robbins
Publication year - 2020
Publication title -
psychology and neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.225
H-Index - 18
eISSN - 1984-3054
pISSN - 1983-3288
DOI - 10.1037/pne0000221
Subject(s) - psychology , serotonergic , glutamatergic , neuroscience , orbitofrontal cortex , modulation (music) , visual cortex , cognitive psychology , audiology , prefrontal cortex , serotonin , glutamate receptor , cognition , chemistry , medicine , receptor , biochemistry , philosophy , aesthetics
Adapting behavior to a dynamic environment requires both steadiness when the environment is stable and behavioral flexibility in response to changes. Much evidence suggests that cognitive flexibility, which can be operationalized in reversal learning tasks, is mediated by cortico-striatal circuitries, with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, and we have previously reported differential roles of lateral (lOFC) and medial (mOFC) regions in a touchscreen serial visual reversal learning task for rats using pharmacological inactivation. Here, we investigated the effects of pharmacological overactivation of these regions using a glutamate transporter 1 (GLT-1) inhibitor, dihydrokainate (DHK), which increases extracellular glutamate by blocking its reuptake. We also tested the impact of antagonism of the serotonin 2A receptor (5-HT 2A R), which modulates glutamate action, in the mOFC and lOFC on the same task. Overactivation induced by DHK produced dissociable effects in the mOFC and lOFC, with more prominent effects in the mOFC, specifically improving performance in the early, perseveration phase. Intra-lOFC DHK increased the number of omitted responses without affecting errors. In contrast, blocking the 5-HT 2A R in the lOFC impaired reversal learning overall, while mOFC 5-HT 2A R blockade had no effect. These results further support dissociable roles of the rodent mOFC and lOFC in deterministic visual reversal learning and indicate that modulating glutamate transmission through blocking the GLT-1 and the 5-HT 2A R have different roles in these two structures.

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