1. ¹Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, CB2 4AT
2. ²Laboratory of Cognitive and Developmental Neuroscience, Department of Neurobiology, The Babraham Institute, Cambridge, CB2 4AT

Correspondence: GJ Hathway, Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, CB2 4AT. E-mail: gareth.hathway@bbsrc.ac.uk

³Current address: Advanced Medicine, 901 Gateway Blvd., South San Fransisco, California, CA 94080 U.S.A.

Received 13 June 2001; Revised 21 August 2001; Accepted 3 September 2001.

Abstract

1. We have used in vivo microdialysis in anaesthetized rats to investigate whether levels of striatal somatostatin (SRIF) can be increased in response to application of the ionotropic glutamate receptor agonists AMPA and NMDA.
2. Application of both AMPA and NMDA (10, 50, 100 and 500 M) for 20 min periods produced concentration-dependent increases in the extracellular levels of SRIF. A 500 M dose of each compound was shown to be the most potent concentration tested, increasing levels of SRIF by 32 fold (NMDA) and 35 fold (AMPA). At lower concentrations (10 M) NMDA failed to evoke significant amounts of SRIF while AMPA increased levels of the peptide 2.3 fold.
3. Application of the respective receptor antagonists APV (NMDA receptor) and DNQX (AMPA receptor) abolished the abilities of the agonists to evoke release of SRIF. Interestingly DNQX abolished the ability of NMDA to evoke release of the peptide as well.
4. The ability of both AMPA and NMDA to evoke increases in the levels of extracellular SRIF further illustrates the reciprocal relationship that exists between SRIF and glutamate in the striatum which impacts particularly on dopaminergic functioning in this region.