Effect of gastrin-releasing peptide on rat hippocampal extracellular GABA levels and seizures in the audiogenic seizure-prone DBA/2 mouse

Gastrin-releasing peptide (GRP), a selective agonist for the BE2 subtype of bombesin receptor, is reported to depolarise GABAergic interneurons in the stratum oriens layer of the hippocampus. Such an action might lead to incr eased extracellular levels of GABA in the hippocampus, and result in an ant i-convulsant effect with this peptide. We have tested this hypothesis by de termining the effect of GRP on extracellular levels of GABA in the ventral hippocampus of the freely moving rat using in vivo microdialysis, and by in tracerebroventricular (i.c.v.) administration of GRP to audiogenic seizure- prone DBA/2 mice prior to exposure to the noise of an electric bell. Follow ing local perfusion in the ventral hippocampus by reverse dialysis GRP (10 mu M) significantly raised levels of GABA in the recovered dialysates by ap proximately 40%. In the seizure studies, GRP (30-300 ng) increased the late ncy to tonic seizure, the number of mice convulsing and reduced the inciden ce of lethality. In both dialysis and seizure studies, the effects of GRP w ere blocked by the selective BB2 receptor antagonist, [D-Phe(6), Leu-NHE13] bombesin (6-13). These experiments provide further functional evidence that activation of the BB2 receptor may modulate neurotransmission in the hippo campus, and that this action may confer anti-convulsant properties on agoni sts acting at the BB2 receptor in the brain. (C) 2000 Elsevier Science B.V. All rights reserved.