Impaired cognitive behavioral flexibility following methamphetamine or high caloric diet consumption: a common 5-HT2C mechanism?

Banks, Matthew L.

doi:10.1038/s41386-018-0243-1

Cited by 2 publications

(1 citation statement)

References 9 publications

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“…Moreover, this apparent opposite effect of WAY163909 administration, decreasing impulsivity in the SSRTT and increasing feeding, may be a result of effects of 5-HT 2C R agonism in different parts of the brain with distinct dissociable functions on behaviour. However, a recent study (35) has demonstrated that agonism of the 5-HT 2C R with WAY163909, affected response control, akin to the improved stopping we have found here, in combination with consumption of a high calorific diet suggesting a relationship between dietary habits and decision-making strategies with 5-HT 2C R at the nexus (36,37).…”

Section: Discussionsupporting

confidence: 50%

Prader–Willi syndrome imprinting centre deletion mice have impaired baseline and 5-HT2CR-mediated response inhibition

Davies

Wilkinson

Isles

et al. 2019

Human Molecular Genetics

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Prader–Willi syndrome (PWS) is a neurodevelopmental disorder caused by deletion or inactivation of paternally expressed imprinted genes on human chromosome 15q11–q13. In addition to endocrine and developmental issues, PWS presents with behavioural problems including stereotyped behaviour, impulsiveness and cognitive deficits. The PWS genetic interval contains several brain-expressed small nucleolar (sno) RNA species that are subject to genomic imprinting, including snord115 that negatively regulates post-transcriptional modification of the serotonin 2C receptor (5-HT2CR) pre-mRNA potentially leading to a reduction in 5-HT2CR function. Using the imprinting centre deletion mouse model for PWS (PWSICdel) we have previously shown impairments in a number of behaviours, some of which are abnormally sensitive to 5-HT2CR-selective drugs. In the stop-signal reaction time task test of impulsivity, PWSICdel mice showed increased impulsivity relative to wild-type (WT) littermates. Challenge with the selective 5-HT2CR agonist WAY163909 reduced impulsivity in PWSICdel mice but had no effect on WT behaviour. This behavioural dissociation in was also reflected in differential patterns of immunoreactivity of the immediate early gene c-Fos, with a blunted response to the drug in the orbitofrontal cortex of PWSICdel mice, but no difference in c-Fos activation in the nucleus accumbens. These findings suggest specific facets of response inhibition are impaired in PWSICdel mice and that abnormal 5-HT2CR function may mediate this dissociation. These data have implications for our understanding of the aetiology of PWS-related behavioural traits and translational relevance for individuals with PWS who may seek to control appetite with the new obesity treatment 5-HT2CR agonist lorcaserin.

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Section: Discussionsupporting

confidence: 50%