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 BB(2) subtype of bombesin receptor, is reported to depolarise GABAergic interneurons in the stratum oriens layer of the hippocampus. Such an action might lead to increased extracellular levels of GABA in the hippocampus, and result in an anti-convulsant effect with this peptide. We have tested this hypothesis by determining the effect of GRP on extracellular levels of GABA in the ventral hippocampus of the freely moving rat using in vivo microdialysis, and by intracerebroventricular (i.c.v.) administration of GRP to audiogenic seizure-prone DBA/2 mice prior to exposure to the noise of an electric bell. Following local perfusion in the ventral hippocampus by reverse dialysis GRP (10 microM) significantly raised levels of GABA in the recovered dialysates by approximately 40%. In the seizure studies, GRP (30-300 ng) increased the latency to tonic seizure, the number of mice convulsing and reduced the incidence of lethality. In both dialysis and seizure studies, the effects of GRP were blocked by the selective BB(2) receptor antagonist, [D-Phe(6), Leu-NHEt(13)]bombesin (6-13). These experiments provide further functional evidence that activation of the BB(2) receptor may modulate neurotransmission in the hippocampus, and that this action may confer anti-convulsant properties on agonists acting at the BB(2) receptor in the brain.
Andrews
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N
Parke-Davis Neuroscience Research Centre, Cambridge University Forvie Site, Robinson Way, Cambridge, UK. nick.andrews@wl.com
Davis
B
B
Gonzalez
M I
MI
Oles
R
R
Singh
L
L
McKnight
A T
AT
D000818:Animals; D004305:Dose-Response Relationship, Drug; D020195:Epilepsy, Reflex / Q000188:drug therapy* / Q000503:physiopathology*; D005110:Extracellular Space / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide / Q000378:metabolism* / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D019886:Gastrin-Releasing Peptide