Opposite effects of two ligands for peripheral type benzodiazepine binding sites, PK 11195 and RO5-4864, in a conflict situation in the rat.
The effects of two drugs acting at the peripheral type benzodiazepine binding sites, PK 11195 and RO5-4864, were examined in shock-induced suppression of drinking in rats. These two compounds have opposite effects : RO5-4864 (3.1-1205 mg/kg i.p.) enhanced whereas PK 11195 (25-50 mg/kg i.p.) decreased the punished responding, and PK 11195 (6.25 mg/kg, a dose which did not alter the punished responding) blocked the proconflict action of RO5-4864 (6.25 and 12.5 mg/kg). The effects of RO5-4864 and PK 11195 were not antagonized by RO15-1788, a selective antagonist of the central benzodiazepine site. In addition, PK 11195 (6.25 mg/kg) did not reverse the proconflict effect of two beta-carbolines : beta-CEE and FG 7142. AS picrotoxin did not change the punished responding, these data imply that the effects of RO5-4864 and PK 11195 on the one hand and those of chlordiazepoxide and beta-carbolines on the other hand are differentially mediated and suggest that the peripheral type benzodiazepine binding sites are involved in this conflict model.
Mizoule
J
J
Gauthier
A
A
Uzan
A
A
Renault
C
C
Dubroeucq
M C
MC
Guérémy
C
C
Le Fur
G
G
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004597:Electroshock; D005442:Flumazenil; D007546:Isoquinolines / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
D001570:Benzodiazepinones; D002243:Carbolines; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D005442:Flumazenil; C035874:FG 7142; C024915:beta-carboline-3-carboxylic acid ethyl ester; C037850:PK 11195