Effects of long-term lithium and desipramine treatment upon clonidine-induced inhibition of /sup 3/H-norepinephrine release from rat hippocampal slices
Long-term treatment with antidepressant agents alters the specific binding of /sup 3/H-clonidine, an alpha/sub 2/ adrenoreceptor agonist, to neural membranes isolated from specific areas of the rat brain. The purpose of the present study was to determine whether these changes in binding of /sup 3/H-clonidine represent an alteration in the functional state of the presynaptic alpha/sub 2/ adrenorecepotr. Hippocampal slices were incubated with /sup 3/H-norepinephrine (/sup 3/H-NE, 330 nM0 for 20 min, washed with fresh buffer for 30 min and then stimulated (4 Hz, 2 msec duration, 2 min) at 12 min intervals. Cumulative concentration-effect curves were determined of /sup 3/H-NE. Rats were injected, i.p., twice daily for 14 days with lithium chloride (105 mg/kg), desipramine HCl (10 mg/kg) or saline. In controls, the EC50 for clonidine was 2.3 +/- 1.0 nM (n = 3). After lithium treatment, the clonidine concentration-effect curve was shifted to the right, and the EC50 as 12.1 +/- 4.3 nM. Desipramine treatment nearly abolished the inhibitory effect of clonidine upon the release of /sup 3/H-NE by field stimulation. These observations indicate that the long-term administration of desipramine and lithium produce a functional subsensitivity of the alpha/sub 2/ adrenoreceptor which regulates norepinephrine release in the rat brain.
- Research Organization:
- Univ. of Michigan, Ann Arbor
- OSTI ID:
- 5278497
- Report Number(s):
- CONF-8604222-; TRN: 86-030434
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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ANTIDEPRESSANTS
BIOLOGICAL EFFECTS
LITHIUM
NORADRENALINE
SECRETION
BIOCHEMICAL REACTION KINETICS
HIPPOCAMPUS
INHIBITION
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ALKALI METALS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
DRUGS
ELEMENTS
HORMONES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
METALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANS
PSYCHOTROPIC DRUGS
REACTION KINETICS
RODENTS
STEROID HORMONES
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques