Panic-like attack induced by microinfusion into the locus coeruleus of antagonists and inverse agonists at GABAA-receptors in rodents.
The microinfusion of drugs inhibiting GABA-ergic transmission into the locus coeruleus (LC) of rats and mice produced a dramatic pattern of behavioural stimulation accompanied by marked electrocortical (ECoG) desynchronization. In rats, unilateral microinfusion into the LC of bicuculline (0.5-4 pmol) produced dose-dependent behavioural stimulation culminating in a panic-like attack, ECoG desynchronization and marked changes in ECoG spectrum power. These effects were prevented by a pretreatment into the same site with muscimol. Similarly, in mice, the microinfusion of ethyl-beta-carboline-3-carboxylate (beta-CCE, 4.1 nmol) into the LC of C57BL/6 mice produced an intense state of behavioural stimulation accompanied by intense stereotyped movements and increased excitability to external stimuli; these effects were prevented by prior microinfusion of diazepam or flumazenil into the same site. In conclusion, the present experiments show that in rodents drug manipulations leading to a decrease in the activity of GABA-benzodiazepine receptor complex in the LC are responsible for the occurrence of panic-like attacks.
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Department of Biology, University of Rome Tor Vergata, Italy.
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David
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D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology; D018756:GABA Antagonists; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010200:Panic / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D002243:Carbolines; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C024915:beta-carboline-3-carboxylic acid ethyl ester; D003975:Diazepam