Short-term rebound anxiolytic effects and long-term changes in platelet benzodiazepine binding after pentylenetetrazole-kindling in two strains of rat.
Although there were no differences in response to an acute injection of pentylenetetrazole (PTZ), there were strain differences in the development of kindled seizures to repeated injections (PTZ; 30 mg/kg 3 times weekly for 13 injections), with Wistar rats reaching stage 4 or 5 of clonic-tonic seizures, but hooded Lister rats reaching only stage 2 or 3 of convulsive waves axially through the body. The strains also reacted differently to a test dose of PTZ (20 mg/kg) one week after the end of kindling, with the Wistar strain showing stage 3 and the Lister strain stage 2 seizures. When the rats were tested 24 h after the end of the kindling injections there was an anxiolytic effect in the social interaction test, in both the low light, familiar and the low light, unfamiliar test conditions that reached significance in the Wistar strain. The Wistar kindled rats showed an anxiolytic effect in the elevated plus-maze test of anxiety when they were tested 24 h after the end of kindling. The anxiolytic effects found 24 h after kindling could not be due to the seizure 24 h earlier, since no changes were found in rats tested 24 h after a single seizure from PTZ (60 mg/kg). When the rats were tested 1 week after the end of kindling there were no changes, compared with vehicle-injected controls, in either test of anxiety. There was no change in benzodiazepine binding in platelets of the kindled Lister rats but there was a significant increase in the kindled Wistar rats 1 week after the end of kindling and also 24 h after a single PTZ seizure. The pattern of increased platelet benzodiazepine binding did not correspond with the time course of rebound anxiolytic effects. However, after kindling it seems that there are long-lasting changes in benzodiazepine binding that are similar to the short-term increases that are found following a single seizure.
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Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London, United Kingdom.
Mabbutt
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Becker
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Gonzalez
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Fluck
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D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D001570:Benzodiazepinones / Q000493:pharmacokinetics; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D007546:Isoquinolines / Q000493:pharmacokinetics; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012919:Social Behavior; D013045:Species Specificity
D001570:Benzodiazepinones; D007546:Isoquinolines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D010433:Pentylenetetrazole; C037850:PK 11195