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

Journal Article · Tue Dec 01 00:00:00 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), Vol. 243:3
• Country of Publication: United States
• Language: English

Related Subjects

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