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1. J Neuroendocrinol. 2012 Feb 17. doi: 10.1111/j.1365-2826.2012.02278.x. [Epub
ahead of print]

Behavioural consequences of P-glycoprotein deficiency in mice, with special focus
on stress related mechanisms.

Schoenfelder Y, Hiemke C, Schmitt U.

Department of Psychiatry and Psychotherapy, University Medical Centre of the
Johannes Gutenberg-University Mainz, Untere Zahlbacher Str. 8, 55131 Mainz,
Germany.

P-glycoprotein (P-gp), an efflux transporter localized in the
blood-brain-barrier, limits the access of multiple xenobiotics to the central
nervous system. Whether it is also implemented in the transport of the endogenous
glucocorticoid corticosterone is a matter of debate. The P-gp knockout mouse
model (abcb1a/b (-/-)) has been shown to differ in the functioning of the
hypothalamus pituitary adrenal (HPA) axis. Here we studied the behaviour of
abcb1a/b (-/-) and wildtype mice with respect to stress-related tests and effects
of corticosterone. Behavioural activities were assessed in the open field test
(OF) for four days, in the forced swimming test (FST) and tail suspension test
(TST) under naïve and stressed conditions. The FST was also conducted after
exogenous corticosterone injection (0.25 and 2.5 mg/kg). Moreover, the elevated
plus maze test (ePM) and the rotarod test were assessed. Brain corticosterone
levels were determined by an immuno-assay and expression of glucocorticoid
receptors (GR) by Western-blot analysis. Abcb1a/1b (-/-) mice showed
significantly decreased brain corticosterone levels and elevated GR expression.
Behavioural analysis revealed a significantly decreased activity in the OF on the
first two days in abcb1a/1b (-/-) mice compared to wildtype mice, but differences
disappeared under habituation. Immobility time in the FST was significantly
decreased in abcb1a/1b (-/-) mice under basal and under stressed conditions,
while immobility in the TST was significantly elevated in these mice under all
conditions. Injection of exogenous corticosterone resulted in significant
reductions of immobility in the FST in abcb1a/1b (-/-) mice, while wildtype mice
did not respond to the same doses. There were no differences in the ePM and
rotarod test. The results demonstrate that a P-gp deficiency has an impact on the
stress-related behaviour, possibly due to differences in HPA-axis feedback
regulation.

Journal of Neuroendocrinology © 2012 Blackwell Publishing.

PMID: 22339976 [PubMed - as supplied by publisher]