Enhanced down regulation of cortical +-propranolol sensitive ( sup 3 H)-DHA binding sites by co-administration of DMI and 5-HT sub 1A partial agonist gepirone

Conference · Mon Feb 26 04:00:00 EST 1990 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5489305

Geissler, M A; Yocca, F D ^[1]

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1. Bristol-Myers Squibb Co., Wallingford, CT (United States)

The putative interrelationship between the noradrenergic and serotonergic systems has been supported by numerous studies. Recently, Dudley et al. (1989) demonstrated significant down regulation of cortical {beta}-adrenergic receptors by co-administration of desipramine (DMI), a norepinephrine uptake inhibitor, and the full 5-HT{sub 1A} agonist 8-OH-DPAT. To this end, the effects of acute and chronic (4 and 14 day) administration of DMI, gepirone, a selective 5-HT{sub 1A} post-synaptic partial agonist, as well as a combination of the two, on cortical ({plus minus})-propranolol sensitive ({sup 3}H)-DHA binding sites were examined in rats. Down regulation was apparent after 4 and 14 day treatment with DMI. However, this was not the case with gepirone. Of particular importance is the demonstration of a greater magnitude of down regulation with co-administration of a greater magnitude of down regulation with co-administration of DMI and gepirone. These results suggests that alteration in rat cortical ({plus minus})-propranolol sensitive ({sup 3}H)-DHA binding sites by noradrenergic uptake inhibitors can be further modulated by selective partial agonist activity at central 5-HT{sub 1A} postsynaptic receptors. Further data on the co-administration of DMI and BMY 7378 (7,9-dioxo-8-(2-(4-{und o}-methoxyphenylpiperazinyl)ethyl)-8-azaspiro(4,5)decane dihydrochloride), a weak partial agonist at postsynaptic 5-HT{sub 1A} receptors, are also presented.

• OSTI ID: 5489305
• Report Number(s): CONF-9004153--
• Conference Information: Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 4:3
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AUTORADIOGRAPHY
AZAARENES
AZOLES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
KINETICS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SEROTONIN
SYMPATHOLYTICS
SYMPATHOMIMETICS
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES