caa a22 4500 469078324 CHVBK 20180323132941.0 cr unu---uuuuu 170328e19921001xx s 000 0 eng 10.1007/BF00171086 doi (NATIONALLICENCE)springer-10.1007/BF00171086 The effect of chronic treatment with peripheral benzodiazepine receptor ligands on behavior and GABAA/benzodiazepine receptors in rat [Elektronische Daten] [Lembit Rägo, Veijo Saano, Timo Auvinen, Aleksander Adojaan, Risto Holma, Mauno Airaksinen] Summary: Rats were twice daily (2 × 10 mg/kg, i.p.) treated for three weeks with the peripheral benzodiazepine (BZ) receptor ligands Ro 5-4864 (4′-chlorodiazepam) and PK 11 195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide). After the first injection there were no differences between the drug-treated and control animals in behavioral tests. After 10 days treatment, the number of sniffings was increased in Ro 5-4864-treated rats. After the last injection, sniffings and ambulations were decreased in PK 11 195-treated animals. The number of rearings and groomings remained unchanged throughout the treatment, and there were no changes in the results in the elevated plus-maze test. Apparently these compounds are devoid of anxiolytic and anxiogenic effects at moderate doses. The effect of 72 a h withdrawal from the above mentioned chronic treatment on peripheral and central BZ receptors as well as on GABAA receptors was studied with receptor binding techniques using 3H-Ro 5-4864, 3H-flumazenil and 3H-muscimol, respectively, as ligands. The number of GABAA and central BZ receptors was lower after Ro 5-4864 treatment, as was the effect of progesterone-induced stimulation of 3H-muscimol binding. The number of peripheral BZ receptors was decreased after Ro 5-4864 and PK 11 195 treatments in the olfactory bulb but not in the cerebral cortex. The chronic treatment with peripheral BZ receptor ligands ] Ro 5-4864 and PK 11 195 produced only little behavioral effects. Ro 5-4864, often presented as an agonist of peripheral BZ receptors, was behaviorally inactive. PK 11 195, often considered to be an antagonist of Ro 5-4864 developed a small sedative action during chronic treatment. The withdrawal from chronic treatment with these ligands similarly affected peripheral BZ receptors but only Ro 5-4864 affected GABAA/BZ receptor complex in the CNS. The present data support the idea that Ro 5-4864 has independent of peripheral BZ receptors effects on GABA, receptors while PK 11 195 is rather a partial agonist than antagonist of peripheral BZ receptors. Springer-Verlag, 1992 Ro 5-4864 nationallicence PK 11 195 nationallicence Chronic treatment nationallicence Behavior withdrawal nationallicence GABAA and benzodiazepine receptors nationallicence Rägo Lembit Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut Saano Veijo Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut Auvinen Timo Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut Adojaan Aleksander Department of Pharmacology, Tartu University, Ülikooli 18, EE-2400, Tartu, Estonia aut Holma Risto Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut Airaksinen Mauno Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/4(1992-10-01), 432-436 0028-1298 346:4<432 1992 346 210 https://doi.org/10.1007/BF00171086 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00171086 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rägo Lembit Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Saano Veijo Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Auvinen Timo Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Adojaan Aleksander Department of Pharmacology, Tartu University, Ülikooli 18, EE-2400, Tartu, Estonia aut NATIONALLICENCE 700 1- Holma Risto Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Airaksinen Mauno Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/4(1992-10-01), 432-436 0028-1298 346:4<432 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer