Effects of histamine and some related compounds on conditioned avoidance response in rats
When histamine (Hi) and other agonists were applied intraventricularly, Hi caused a dose-dependent inhibition of the avoidance response in rats; its ED50 was 3.60 ..mu..g. l-methylHi, l-methylimidazole acetic acid and imidazole acetic acid which are major metabolites of Hi produced no inhibitory effect even at 50 ..mu..g. H/sub 1/-agonists (2-methylHi and 2-thiazolylethylamine) also depressed the avoidance response; their dose-response lines run parallel to that of Hi. The depressant effects of H/sub 2/-agonists (4-methylHi and dimaprit) were relatively weak; their dose-response lines were not parallel to that of Hi. When antagonists were pretreated intravenously, Hi action was clearly antagonized by diphehydramine and pyrilamine, but not by cimetidine or ranitidine. Intraventricular injection of Hi mixed with cimetidine or ranitidine did not change the effect induced by Hi alone. The avoidance response was not affected by noradrenaline, dopamine or 5-hydroxytryptamine. Although acetylcholine (ACh) suppressed the avoidance response dose-dependently, its effect was much weaker than that of Hi. Pretreatment with cholinergic blocking drugs (atropine and scopolamine) antagonized ACh action but not Hi action. From these results, it is assumed that the inhibitory effect of Hi on the avoidance response is preferentially linked to the H/sub 1/-receptor. After intraventricular application of /sup 3/H-Hi, the highest radioactivity was determined in the hypothalamus. 21 references, 4 figures, 4 tables.
- Research Organization:
- Okayama Univ., Japan
- OSTI ID:
- 5079929
- Journal Information:
- Life Sci.; (United States), Vol. 37:21
- Country of Publication:
- United States
- Language:
- English
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HISTAMINE
BIOLOGICAL EFFECTS
RATS
AVOIDANCE
RECEPTORS
BIOCHEMICAL REACTION KINETICS
ACETYLCHOLINE
DOPAMINE
DOSE-RESPONSE RELATIONSHIPS
EXPERIMENTAL DATA
HYPOTHALAMUS
METABOLITES
NORADRENALINE
TRYPTAMINES
ADRENAL HORMONES
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BEHAVIOR
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DATA
DRUGS
ESTERS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
IMIDAZOLES
INDOLES
INFORMATION
KINETICS
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
PHENOLS
POLYPHENOLS
PYRROLES
QUATERNARY COMPOUNDS
REACTION KINETICS
RODENTS
STEROID HORMONES
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques