MGlu5 antagonism impairs exploration and memory of spatial and non-spatial stimuli in rats.
Metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in memory processing in some but not all learning tasks. The reason why this receptor is involved in some tasks but not in others remains to be determined. The present experiments using rats examined effects of the mGlu5-antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP)--applied systemically i.p. (1-10mg/kg) or bilaterally into the prelimbic cortex (1-10 microg)---on the ability of rats to explore and remember new stimuli. A cross-maze, open field, and object recognition task were used to evaluate exploration and memory and it was found that: (1) locomotion during exploration of spatial environments and exploration time at novel objects were reduced by i.p. but not by prelimbic administration of MPEP, (2) spatial short-term memory was impaired in cross-maze and object discrimination was reduced after both types of administration, (3) long-term retention of spatial conditioning in the cross-maze was inhibited after i.p. applications which (4) also inhibited spontaneous alternation performance during maze-exploration. Reduced exploratory locomotion and exploration time after i.p. injections may have contributed to the observed retention impairments. However, the fact that prelimbic administration of MPEP inhibited retention without reducing exploration shows that memory formation was also impacted directly by prelimbic mGlu5 in both spatial and non-spatial learning.
Christoffersen
Gert R J
GR
Department of Biology, August Krogh Building, University of Copenhagen, DK-2100 Copenhagen, Denmark. gert.christoffersen@gmail.com
Simonyi
Agnes
A
Schachtman
Todd R
TR
Clausen
Bettina
B
Clement
David
D
Bjerre
Vicky K
VK
Mark
Louise T
LT
Reinholdt
Mette
M
Schmith-Rasmussen
Kati
K
Zink
Lena V B
LV
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005106:Exploratory Behavior / Q000187:drug effects*; D018756:GABA Antagonists / Q000008:administration & dosage; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced*; D046709:Pattern Recognition, Physiological / Q000187:drug effects; D010852:Picrotoxin / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception / Q000187:drug effects*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010852:Picrotoxin; D011725:Pyridines; C121465:6-methyl-2-(phenylethynyl)pyridine