Effects of the mGluR2/3 agonist LY354740 on computerized tasks of attention and working memory in marmoset monkeys.
BACKGROUND
LY354740 is a recently developed metabotropic glutamatergic receptor 2 and 3 (mGluR2/3) agonist. A high density of mGluR2 has been reported in terminal fields of the perforant path in rodents and humans, suggesting its involvement in cognitive functions mediated by the temporal lobe, including memory. A small number of in vivo studies in rodents have assessed the effects of LY354740 on memory tasks, reporting the induction of impaired memory for spatial orientation in a water maze task and for delayed match and non-match to position in an operant version of these tasks.


OBJECTIVE
In the present primate study, we used radioautography to describe the distribution and intensity of (3)H-LY354740 binding in the hippocampal formation of the common marmoset monkey (Callithrix jacchus) relative to the rat. In the major, in vivo part of the study, the effects of systemic LY354740 on computerized tasks of attention and memory were investigated.


METHODS
Adult common marmosets were trained to perform a five-choice serial reaction time (5-CSRT) task and a concurrent delayed match-to-position (CDMP) task from the Cambridge Neuropsychological Automated test Battery (CANTAB). Filter tests of LY354740 effects on motor dexterity and motivation for reward revealed high inter-individual variation in sensitivity; therefore, on the 5-CSRT, subjects were tested at a dose range of 3--10 mg/kg, and on the CDMP, subjects were tested at 1--3 or 3--10 mg/kg.


RESULTS
Radioautography revealed a relatively low level of (3)H-LY354740 binding in the marmoset hippocampal formation compared to the rat. Despite low binding, LY354740 reduced sustained-attention accuracy in the 5-CSRT, and reduced accuracy in two stages of the CDMP.


CONCLUSIONS
The current study provides novel evidence for the importance of mGluR2/3 in the regulation of primate cognitive functioning.
Spinelli
Simona
S
Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Ballard
Theresa
T
Gatti-McArthur
Silvia
S
Richards
Grayson J
GJ
Kapps
Martin
M
Woltering
Thomas
T
Wichmann
Jurgen
J
Stadler
Heinz
H
Feldon
Joram
J
Pryce
Christopher R
CR
D000818:Animals; D001288:Attention / Q000187:drug effects*; D001345:Autoradiography; D015153:Blotting, Western; D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D002144:Callithrix; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D008568:Memory / Q000187:drug effects*; D009483:Neuropsychological Tests; D011930:Reaction Time / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*
D001643:Bridged Bicyclo Compounds; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C104753:eglumetad