Evidence that somatostatin sst(2) receptors mediate striatal dopamine release

1 Somatostatin (SRIF) is a cyclic tetradecapeptide present in medium-sized aspiny interneurones in the rat striatum. We have previously shown that exo genous SRIF potently stimulates striatal dopamine (DA) release via a glutam ate-dependent mechanism. We now report the ability of the selective sst? re ceptor agonist, BIM-23027, to mimic this effect of SRIF. 2 In vivo microdialysis studies were performed in anaesthetized male Wistar rats. in most experiments, compounds were administered by retrodialysis in to the striatum for 15 min periods, 90 min and 225 min after sampling comme nced, with levels of neurotransmitters being measured by HPLC with electroc hemical and fluorescence detection. 3 BIM-23027 (50 and 100 nM) stimulated DA release with extracellular levels increasing by up to 18 fold. 4 Prior retrodialysis of BIM-23027 (50 nM) abolished the effects of subsequ ent administration of SRIF (100 nM). 5 The agonist effects of both BIM-23027 and SRIF were abolished by the sele ctive sst(2) receptor antagonist, L-Tyr(8)-CYN-154806 (100 nM). 6 The AMPA/kainate receptor antagonist, DNQX (100 mu M), abolished the agon ist effects of BIM-23027 as previously shown for SRIF. 7 This study provides evidence that the sat? receptor mediates the potent d opamine-releasing actions observed with SRIF in the rat striatum. Dopamine release evoked by both peptides appears to be mediated indirectly via a glu tamatergic pathway. Other subtype-specific somatostatin receptor ligands we re unable to elicit any effects and therefore we conclude that no other som atostatin receptor types are involved in mediating the dopamine-releasing a ctions of SRIF in the striatum.