The effect of chronic treatment with peripheral benzodiazepine receptor ligands on behavior and GABAA/benzodiazepine receptors in rat.

Article date: 1992/10/1

PubMed ID: 2159125

Journal name: Naunyn-Schmiedeberg's archives of pharmacology (ISSN: 0028-1298)


Rats were twice daily (2 x 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-carbox ami de). 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List: Rägo L, Saano V, Auvinen T, Adojaan A, Holma R, Airaksinen M M

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Benzodiazepinones; Convulsants; Isoquinolines; Receptors, GABA-A; Muscimol; 4'-chlorodiazepam; PK 11195;

Mesh terms: Animals; Behavior, Animal/drug effects; Benzodiazepinones/adverse effects; Brain/drug effects; Convulsants/pharmacology; Injections, Intraperitoneal; Isoquinolines/adverse effects; Male; Muscimol/metabolism; Rats; Rats, Wistar; Receptors, GABA-A/drug effects; Substance Withdrawal Syndrome;

Citations: - 2155149

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