Anxiolytic-like effects of the selective metabotropic glutamate receptor 5 antagonist MPEP after its intra-amygdaloid microinjection in three different non-conditioned rat models of anxiety.
The intercalated islands, clusters of dopamine D1-rich GABAergic neurons, are interposed between the basolateral and central nuclei of the amygdala, and control the traffic of nerve impulses between these two structures. Metabotropic glutamate receptor 5- (mGluR5)-like immunoreactivity was studied by immunohistochemistry in this part of the amygdala and was found to be mainly restricted to the central and basolateral nuclei and to a lesser extent to the medial paracapsular intercalated islands. The role of the metabotropic glutamate receptor 5 in the modulation of anxiety has been studied in this region by microinjection of small volumes of the mGluR5 antagonist 2-methyl-6(phenylethenyl) pyridine (MPEP), with restricted diffusion from its injection site, into the rostral amygdala near the basolateral and central amygdaloid nuclei and the intercalated islands, and the behavior of the animals was evaluated using three non-conditioned models of anxiety. Anxiolytic-like effects were observed after MPEP administration in all tests used. In the White and Black Box test, MPEP (2 nmol per side) significantly increased the time spent in the white compartment of the box. In line with these results, MPEP (8 nmol per side) increased the exploration of the open arms of the Elevated Plus-Maze. Burying behavior latency was increased and burying behavior itself was decreased in the Shock-Probe Burying test. It is suggested that anxiolytic effects of MPEP may be mediated by blockade of mGluR5 in the basolateral and/or central amygdaloid nuclei, reducing glutamate transmission in the basolateral amygdaloid nuclei and glutamate output from the central amygdala.
Pérez de la Mora
Miguel
M
Department of Biophysics, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-253, México 04510 DF México. mperez@ifc.unam.mx
Lara-García
Daniel
D
Jacobsen
Kirsten X
KX
Vázquez-García
Mariana
M
Crespo-Ramírez
Minerva
M
Flores-Gracia
Candy
C
Escamilla-Marvan
Edgardo
E
Fuxe
Kjell
K
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D003214:Conditioning, Classical; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008845:Microinjections; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
D014151:Anti-Anxiety Agents; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine