TY - JOUR
T1 - Anxiety-like behavior of prenatally stressed rats is associated with a selective reduction of glutamate release in the ventral hippocampus
AU - Marrocco, Jordan
AU - Mairesse, Jérôme
AU - Ngomba, Richard Teke
AU - Silletti, Viviana
AU - Van Camp, Gilles
AU - Bouwalerh, Hammou
AU - Summa, Maria
AU - Pittaluga, Anna
AU - Nicoletti, Ferdinando
AU - Maccari, Stefania
AU - Morley-Fletcher, Sara
PY - 2012/11/28
Y1 - 2012/11/28
N2 - Abnormalities of synaptic transmission and plasticity in the hippocampus represent an integral part of the altered programming triggered by early life stress. Prenatally restraint stressed (PRS) rats develop long-lasting biochemical and behavioral changes, which are the expression of an anxious/depressive-like phenotype. We report here that PRS rats showed a selective impairment of depolarization- or kainate-stimulated glutamate and [3H]D-aspartate release in the ventral hippo campus, a region encoding memories related to stress and emotions. GABA release was un affected in PRS rats. As a consequence of reduced glutamate release, PRS rats were also highly resistant to kainate-induced seizures. Abnormalities of glutamate release were associated with large reductions in the levels of synaptic vesicle-related proteins, such as VAMP (synaptobrevin), syntaxin-1, synaptophysin, synapsin Ia/b and IIa, munc-18, and Rab3A in the ventral hippocampus of PRS rats. Anxiety-like behavior in male PRS (and control) rats was inversely related to the extent of depolarization-evoked glutamate release in the ventral hippocampus. A causal relationship between anxiety-like behavior and reduction in glutamate release was demonstrated usingamixtureofthemGlu2/3 receptor antagonist, LY341495, and the GABAB receptor antagonist, CGP52432, which was shown to amplify depolarization-evoked [3H]D-aspartate release in the ventral hippocampus. Bilateral micro infusion of CGP52432 plus LY341495 in the ventral hippocampus abolished anxiety-like behavior in PRS rats. These findings indicate that an impairment of glutamate release in the ventral hippocampus is a key component of the neuro plastic program induced by PRS, and that strategies aimed at enhancing glutamate release in the ventral hippocampus correct the "anxious phenotype" caused by early life stress.
AB - Abnormalities of synaptic transmission and plasticity in the hippocampus represent an integral part of the altered programming triggered by early life stress. Prenatally restraint stressed (PRS) rats develop long-lasting biochemical and behavioral changes, which are the expression of an anxious/depressive-like phenotype. We report here that PRS rats showed a selective impairment of depolarization- or kainate-stimulated glutamate and [3H]D-aspartate release in the ventral hippo campus, a region encoding memories related to stress and emotions. GABA release was un affected in PRS rats. As a consequence of reduced glutamate release, PRS rats were also highly resistant to kainate-induced seizures. Abnormalities of glutamate release were associated with large reductions in the levels of synaptic vesicle-related proteins, such as VAMP (synaptobrevin), syntaxin-1, synaptophysin, synapsin Ia/b and IIa, munc-18, and Rab3A in the ventral hippocampus of PRS rats. Anxiety-like behavior in male PRS (and control) rats was inversely related to the extent of depolarization-evoked glutamate release in the ventral hippocampus. A causal relationship between anxiety-like behavior and reduction in glutamate release was demonstrated usingamixtureofthemGlu2/3 receptor antagonist, LY341495, and the GABAB receptor antagonist, CGP52432, which was shown to amplify depolarization-evoked [3H]D-aspartate release in the ventral hippocampus. Bilateral micro infusion of CGP52432 plus LY341495 in the ventral hippocampus abolished anxiety-like behavior in PRS rats. These findings indicate that an impairment of glutamate release in the ventral hippocampus is a key component of the neuro plastic program induced by PRS, and that strategies aimed at enhancing glutamate release in the ventral hippocampus correct the "anxious phenotype" caused by early life stress.
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U2 - 10.1523/JNEUROSCI.1040-12.2012
DO - 10.1523/JNEUROSCI.1040-12.2012
M3 - Article
C2 - 23197707
AN - SCOPUS:84870175105
VL - 32
SP - 17143
EP - 17154
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 48
ER -