Effects of RU33368, a low affinity ligand for neuronal benzodiazepine receptors, on rodent behaviours and GABA-mediated synaptic transmission in rat cerebellar slices.
1. The effects of the low affinity benzodiazepine receptor ligand RU33368 were studied on rodent behaviours and on GABA-mediated synaptic transmission in rat cerebellar slices. 2. RU33368 inhibited stress induced ultrasounds in rat pups without inducing marked muscle relaxation. RU33368 also enhanced operant responding in rats that had been suppressed by mild footshock. These effects of RU33368 in these two models of anxiety were both blocked by the benzodiazepine antagonist Ro15-1788 (flumazonil). 3. In cerebellar slices RU33368 enhanced stimulus-induced synaptic inhibition of Purkinje layer cells with a minimal effective concentration in the order of 1 microM. The classical benzodiazepine agonist RU32007 was approx. 10 times more potent. This action of RU33368 was blocked by Ro15-1788. 4. The minimal effective concentration of RU33368 fully blocked the effect of RU32007 in 2 of 4 cells tested and partially antagonized it in a third cell. 5. These data suggest that RU33368 is a partial agonist at benzodiazepine receptors and this, at least in part, explains its non-sedative anxiolytic behavioural profile.
Gardner
C R
CR
Roussel Laboratories Ltd, Covingham, Swindon, U.K.
Ward
R A
RA
Deacon
R M
RM
Bagust
J
J
Walker
R J
RJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003220:Conflict, Psychological; D005442:Flumazenil / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D010069:Oxadiazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D013315:Stress, Psychological / Q000378:metabolism; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D008024:Ligands; D010069:Oxadiazoles; D011743:Pyrimidines; D011963:Receptors, GABA-A; C079323:RU 33368; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid