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Effects of the mGluR2/3 agonist LY354740 on computerized tasks of attention and working memory in marmoset monkeys

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Abstract

Rationale

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 3H-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 3H-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.

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Acknowledgements

We are extremely grateful to Silvana Ressegatti and Jeanne Michel for marmoset care, Guy Higgins for insightful discussions, and to Giancarlo Tomio for writing the PERL computer programmes for analysis of the results output generated by the CANTAB software. We are also extremely grateful to Dr. Huguenin, Jurg Messer, Jennifer Beck and Petra Paszkiewicz for technical support in neuroanatomical studies. Simona Spinelli was in receipt of a Studentship funded by F. Hoffmann La Roche, Basel, Switzerland, and additional support was provided by the Swiss Federal Institute of Technology Zurich.

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Authors and Affiliations

  1. Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, 8603, Schwerzenbach, Switzerland

    Simona Spinelli, Joram Feldon & Christopher R. Pryce

  2. F. Hoffmann-La Roche AG, Pharmaceuticals Division, CNS-Preclinical Research, Grenzacherstrasse, 4070, Basel, Switzerland

    Theresa Ballard, Silvia Gatti-McArthur, Grayson J. Richards, Martin Kapps, Thomas Woltering, Jurgen Wichmann & Heinz Stadler

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  1. Simona Spinelli
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  2. Theresa Ballard
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  3. Silvia Gatti-McArthur
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  4. Grayson J. Richards
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  6. Thomas Woltering
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  9. Joram Feldon
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  10. Christopher R. Pryce
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Correspondence to Christopher R. Pryce.

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Spinelli, S., Ballard, T., Gatti-McArthur, S. et al. Effects of the mGluR2/3 agonist LY354740 on computerized tasks of attention and working memory in marmoset monkeys. Psychopharmacology 179, 292–302 (2005). https://doi.org/10.1007/s00213-004-2126-x

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  • DOI: https://doi.org/10.1007/s00213-004-2126-x

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