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Br J Pharmacol. 2016 Jul;173(13):2147-61. doi: 10.1111/bph.13484. Epub 2016 Apr 21.

Alterations in pharmacological and behavioural responses in recombinant mouse line with an increased predisposition to catalepsy: role of the 5-HT1A receptor.

Author information

1
Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia.
2
Cellular Neurophysiology, Hannover Medical School, Hannover, Germany.

Abstract

BACKGROUND AND PURPOSE:

One important syndrome of psychiatric disorders in humans is catalepsy. Here, we created mice with different predispositions to catalepsy and analysed their pharmacological and behavioural properties.

EXPERIMENTAL APPROACH:

Two mouse lines, B6-M76C and B6-M76B, were created by transfer of the main locus of catalepsy containing the 5-HT1A receptor gene to the C57BL/6 genetic background. Behaviour, brain morphology, expression of key components of the serotoninergic system, and pharmacological responses to acute and chronic stimulation of the 5-HT1A receptor were compared.

KEY RESULTS:

B6-M76B mice were not cataleptic, whereas 14% of B6-M76C mice demonstrated catalepsy and decreased depressive-like behaviour. Acute administration of the 5-HT1A receptor agonist 8-OH-DPAT resulted in dose-dependent hypothermia and in decreased locomotion in both lines. Chronic 8-OH-DPAT administration abolished the 5-HT1A receptor-mediated hypothermic response in B6-M76C mice and increased locomotor activity in B6-M76B mice. In addition, 5-HT metabolism was significantly reduced in the hippocampus of B6-M76C mice, and this effect was accompanied by an increased expression of the 5-HT1A receptor.

CONCLUSIONS AND IMPLICATIONS:

Our findings indicate that transfer of the main locus of hereditary catalepsy containing the 5-HT1A receptor from CBA mice to the C57BL/6 genetic background led to increased postsynaptic and decreased presynaptic functional responses of the 5-HT1A receptor. This characteristic establishes the B6-M76C line as an attractive model for the pharmacological screening of 5-HT1A receptor-related drugs specifically acting on either pre- or postsynaptic receptors.

LINKED ARTICLES:

This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.

PMID:
27004983
PMCID:
PMC4908196
DOI:
10.1111/bph.13484
[Indexed for MEDLINE]
Free PMC Article

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