Involvement of group II metabotropic glutamate receptors in stress-induced behavioural sensitization.
BACKGROUND
A short session of repeated foot shocks in rats causes long-lasting sensitization of behavioural, hormonal and autonomic responses to novel stressful challenges. The behavioural sensitization can be reduced by anxiolytics and mimics aspects of stress-induced changes in patients with post-traumatic stress disorder.


OBJECTIVE
The aim of this study was to test the efficacy of a group II metabotropic glutamate receptor (mGluR) agonist and assess altered brain mGluR receptor expression in shock-sensitized rats.


METHODS
Male Wistar rats were exposed to a 15-min session with ten 6-s foot shocks (preshocked). One and 2 weeks later, rats were intraperitoneally injected with the group II metabotropic glutamate receptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) or vehicle, and 30 min later exposed to 5 min of 85 dB noise. For in situ hybridization with probes for mGluR1, mGluR2, mGluR3 and mGluR5, preshocked and control rats were killed under basal conditions 2 weeks after foot shocks and their brains cryosectioned.


RESULTS
APDC had no clear effect in controls, but dose-dependently reduced high immobility and increased low locomotion and rearing seen in preshocked rats to the levels of controls. mGluR3 expression was increased in the basolateral nucleus of the amygdala, and mGluR2 expression was increased in the agranular insular cortex of preshocked rats compared to controls.


CONCLUSIONS
Shock-induced behavioural sensitization in rats is reduced by acute treatment with a group II metabotropic glutamate receptor agonist. This effect may depend on the increased expression of amygdala mGluR3, which could be hypothesized as an endogenous mechanism to counteract stress-induced neuronal sensitization.
Stam
Rianne
R
Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Center Utrecht, Utrecht, The Netherlands. r.stam@med.uu.nl
de Lange
Robert P J
RP
Graveland
Haitske
H
Verhave
Peternella S
PS
Wiegant
Victor M
VM
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005528:Foot; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000502:physiology; D013315:Stress, Psychological / Q000378:metabolism*
C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D018094:Receptors, Metabotropic Glutamate; D011392:Proline