Differential effects of diazepam and MPEP on habituation and neuro-behavioural processes in inbred mice.
BACKGROUND
Previous studies have demonstrated a profound lack of habituation in 129P3 mice compared to the habituating, but initially more anxious, BALB/c mice. The present study investigated whether this non-adaptive phenotype of 129P3 mice is primarily based on anxiety-related characteristics.


METHODS
To test this hypothesis and extend our knowledge on the behavioural profile of 129P3 mice, the effects of the anxiolyticdiazepam (1, 3 and 5 mg/kg) and the putative anxiolytic metabotropic glutamate receptor 5 (mGlu5R) antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP, 3, 10 and 30 mg/kg) treatment on within-trial (intrasession) habituation, object recognition (diazepam: 1 mg/kg; MPEP 10 mg/kg) and on the central-nervous expression of the immediate early gene c-Fos (diazepam: 1 mg/kg; MPEP 10 mg/kg) were investigated.


RESULTS
Behavioural findings validated the initially high, but habituating phenotype of BALB/c mice, while 129P3 mice were characterized by impaired intrasession habituation. Diazepam had an anxiolytic effect in BALB/c mice, while in higher doses caused behavioural inactivity in 129P3 mice. MPEP revealed almost no anxiolytic effects on behaviour in both strains, but reduced stress-induced corticosterone responses only in 129P3 mice. These results were complemented by reduced expression of c-Fos after MPEP treatment in brain areas related to emotional processes, and increased c-Fos expression in higher integrating brain areas such as the prelimbic cortex compared to vehicle-treated 129P3 mice.


CONCLUSIONS
These results suggest that the strain differences observed in (non)adaptive anxiety behaviour are at least in part mediated by differences in gamma-aminobutyric acid- A and mGluR5 mediated transmission.
Department of Animals in Science and Society, Division of Animal Welfare and Laboratory Animal Science, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 Utrecht, CM, The Netherlands. ambersalomons@gmail.com
Amber R
AR
Salomons
Nathaly Espitia
NE
Pinzon
Hetty
H
Boleij
Susanne
S
Kirchhoff
Saskia S
SS
Arndt
Rebecca E
RE
Nordquist
Lothar
L
Lindemann
Georg
G
Jaeschke
Will
W
Spooren
Frauke
F
Ohl
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology*; D006185:Habituation, Psychophysiologic / Q000187:drug effects* / Q000235:genetics*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D011725:Pyridines / Q000494:pharmacology*; D011897:Random Allocation
D011725:Pyridines; C121465:6-methyl-2-(phenylethynyl)pyridine; D003975:Diazepam