Serotonergic modulation of cognitive flexibility in rodents
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EGINITION HOSPITAL, UNIVERSITY OF ATHENS, MEDICAL SCHOOL, PSYCHIATRY, Greece
Cognitive flexibility is dependent upon the orbitofrontal cortex (OFC). Serotonin (5-HT) is strongly implicated as well. However, there is little information on the role of different 5-HT receptors in reversal learning. This presentation will show a series of experiments in rodents implicating specific 5-HT receptors in the same ability. Specifically: Experiments 1-2 investigated the effects of systemic administration of the 5-HT2A receptor antagonist M100907 and the 5-HT2C receptor antagonist SB242084 on an instrumental two-lever spatial discrimination and serial spatial reversal learning task. Experiments 3-8: The effects of SB242084 and M100907 infusions within the OFC, medial prefrontal cortex (mPFC) and nucleus accumbens (nAc) were examined in the same task.
Experiments 1-2: Neither M100907 nor SB242084 altered performance during spatial discrimination and retention of the previously reinforced contingencies. M100907 significantly impaired reversal learning by increasing both trials to criterion (only at the highest dose) and incorrect responses in Reversal 1, a pattern of behaviour manifested as increased perseverative responding on the previously reinforced lever. In contrast, SB242084 improved reversal learning by decreasing trials and incorrect responses to criterion in Reversal 1, with significantly fewer perseverative errors. Experiment 3-5: Infusions of SB242084 within the OFC, but not mPFC or nAc, dose-dependently facilitated reversal learning in the same way as in Experiment 2. Experiments 6-8: No effects were noted with infusions of M100907 within the same three brain regions.
These data support the view that 5-HT2A and 5-HT2C receptors have distinct roles in cognitive flexibility and response inhibition, contrasting with published data on impulsive responding. The improved performance in reversal learning observed following 5-HT2C receptor antagonism suggests these receptors may offer the potential for therapeutic advances in neuropsychiatric disorders where cognitive deficits are a feature, including OCD, and that this effect may be mediated by 5-HT2C receptors within the OFC.
Keywords:
Serotonin,
5-HT2A receptor,
5-HT2C receptors,
OCD,
perseveration,
OFC
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
BOULOUGOURIS
V
(2013). Serotonergic modulation of cognitive flexibility in rodents.
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00010
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Received:
31 Mar 2013;
Published Online:
11 Apr 2013.
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Correspondence:
Dr. VASILEIOS BOULOUGOURIS, EGINITION HOSPITAL, UNIVERSITY OF ATHENS, MEDICAL SCHOOL, PSYCHIATRY, ATHENS, Greece, vboulougouris@googlemail.com