Changes in gamma-aminobutyric acid release induced by topical administration of drugs affecting its metabolism and receptors: studies in freely moving guinea pigs with epidural cups.
The effect of local application of drugs affecting gamma-aminobutyric acid metabolism and receptors on cortical aminoacid release has been investigated in freely-moving guinea pigs equipped with epidural cups. Topical treatment with gamma-aminobutyric acid reuptake and/or metabolism inhibitors (alone and in combination) produced a slow and progressive increase in cortical aminoacid release. The inhibition of gamma-aminobutyric acid-transaminase with ethanolamino-O-sulphate seemed to be a suitable procedure for enhancing the gamma-aminobutyric acid efflux without interfering with its autoreceptor-mediated negative feedback, tested with the gamma-aminobutyric acid agonist (+/-)baclofen and antagonist phaclofen. A substantial part of the gamma-aminobutyric acid outflowing from the cortex was of neuronal origin since tetrodotoxin halved the basal efflux in the presence of gamma-aminobutyric acid reuptake and/or metabolism inhibitors. These results, considered together, indicate that the epidural cup technique may be a useful approach to study changes in cortical gamma-aminobutyric acid release induced by drugs acting on gabaergic transmission and directly applied on the surface of the cortex.
Tanganelli
S
S
Department of Pharmacology, University of Ferrara, Italy.
Ferraro
L
L
Bianchi
C
C
Beani
L
L
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004824:Epidural Space; D004983:Ethanolamines / Q000494:pharmacology*; D005246:Feedback; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D015091:beta-Alanine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D004983:Ethanolamines; D009557:Nipecotic Acids; D011963:Receptors, GABA-A; C052329:phaclofen; D015091:beta-Alanine; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; C020619:ethanolamine O-sulfate; D012964:Sodium; D000612:4-Aminobutyrate Transaminase; D001418:Baclofen; D002118:Calcium; D009638:Norepinephrine