Behavioral studies with anxiolytic drugs. IV. Serotonergic involvement in the effects of buspirone on punished behavior of pigeons

Journal Article · Tue Dec 01 04:00:00 EST 1987 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5471530

Witkin, J M; Mansbach, R S; Barrett, J E; Bolger, G T; Skolnick, P; Weissman, B

Interactions of the nonbenzodiazepine anxiolytic, buspirone, with serotonin (5-HT) were studied using behavioral and neurochemical procedures. Punished responding was studied in pigeons as this behavior is a generally acknowledged preclinical predictor of anxiolytic activity and because buspirone increases punished responding of pigeons with greater potency and efficacy than in other species. Keypeck responses were maintained under either fixed-interval or fixed-ratio schedules of food presentation; every 30th response produced a brief electric shock and suppressed responding (punishment). Buspirone (0.1-5.6 mg/kg i.m.) produced dose-related increases in punished responding which reached a maximum at 1 mg/kg. A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects of buspirone without having behavioral effects of their own. The characteristics of (/sup 3/H)-5-HT binding in pigeon brain membranes were similar to results reported in mammalian brain. Neither buspirone, MJ-13805 (gepirone, a related analog), nor MJ-13653 (a buspirone metabolite), significantly affected (/sup 3/H)-5-HT binding and none of the compounds appreciably inhibited uptake of (/sup 3/H)-5-HT into pigeon cerebral synaptosomes. Hill coefficients significantly less than unity for all drugs except 5-HT suggested multiple serotonergic binding sites for buspirone and analogs. Buspirone and MJ-13805 (1 nM) inhibited (/sup 3/H)ketanserin binding (a measure of 5-HT2 binding sites) in pigeon cerebrum with Ki values above 10(-6) M. The number of (/sup 3/H)ketanserin binding sites was estimated to be 109 fmol/mg of protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat cerebrum.

• Research Organization: Uniformed Services Univ. of the Health Sciences, Bethesda, MD
• OSTI ID: 5471530
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 243:3; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZINES
AZOLES
BEHAVIOR
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIRDS
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PIGEONS
PROTEINS
PSYCHOTROPIC DRUGS
PYRAZINES
PYRIMIDINES
PYRROLES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RECEPTORS
SEROTONIN
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRANQUILIZERS
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES