ABSTRACT
The neuroprotective effect of melatonin against the quinolinic acid-induced degeneration of rat hippocampal neurons was investigated. Three groups of rats were given intrahippocampal injections of either; saline, quinolinic acid or i.p. injections of melatonin prior to and after being injected with quinolinic acid. On the fifth day after the intrahippocampal injections the brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor binding studies. The results show that melatonin protects hippocampal neurons from quinolinic acid-induced neurodegeneration and partially prevents the decrease in glutamate receptor numbers caused by quinolinic acid. Thus, melatonin has the potential to reduce hippocampal neuronal damage induced by neurotoxins such as quinolinic acid.
Subject(s)
Antioxidants/pharmacology , Hippocampus/drug effects , Melatonin/pharmacology , Quinolinic Acid/toxicity , Animals , Drug Interactions , Male , Neurons/drug effects , Neurons/metabolism , Rats , Rats, Wistar , Receptors, Glutamate/drug effects , Receptors, Glutamate/metabolism , Receptors, N-Methyl-D-Aspartate/drug effects , Receptors, N-Methyl-D-Aspartate/metabolismSubject(s)
Apomorphine/metabolism , Corpus Striatum/metabolism , Melatonin/pharmacology , Motor Activity/drug effects , Animals , Corpus Striatum/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Huntington Disease/chemically induced , Hydroxydopamines , Male , Melatonin/administration & dosage , Oxidopamine , Parkinson Disease, Secondary/chemically induced , Quinolinic Acid , Quinolinic Acids , Rats , Rats, Inbred StrainsABSTRACT
Wistar rats show a circadian variation in their response to stress. Pinealectomy exacerbates stress-induced gastric ulceration in rats. This effect is counteracted by melatonin administration.
Subject(s)
Peptic Ulcer/physiopathology , Pineal Gland/physiology , Stress, Physiological/physiopathology , Animals , Circadian Rhythm , Cold Temperature , Female , Melatonin/pharmacology , Rats , Rats, Inbred StrainsABSTRACT
Prior melatonin administration (1,5 and 10 mg/kg b. wt) causes a significant reduction in gastric ulceration induced in male rats by restraint immobilization in the presence of low temperatures.
Subject(s)
Melatonin/pharmacology , Stomach Ulcer/etiology , Stress, Physiological/complications , Animals , Male , Melatonin/administration & dosage , Rats , Rats, Inbred Strains , Restraint, Physical , Stomach Ulcer/prevention & controlABSTRACT
Anticholinergic activity of a number of tricyclic antidepressives and nomifensine was demonstrated and their order of affinity for the cholinergic receptors of rat jejunum was determined. The influence of ethinyl estradiol and a conjugated estrogen product, Premarin on the binding of several tricyclic antidepressives to the hepatic mixed function oxidase system was investigated. The influence of these steroids on the metabolism of the antidepressives was evaluated and ethinyl estradiol was shown to have a marked influence on the metabolism of the antidepressives studied, while conjugated estrogens were shown to have little effect.
Subject(s)
Antidepressive Agents, Tricyclic/administration & dosage , Estrogens, Conjugated (USP)/administration & dosage , Ethinyl Estradiol/administration & dosage , Liver/metabolism , Receptors, Cholinergic/metabolism , Animals , Antidepressive Agents, Tricyclic/metabolism , Drug Interactions , Female , Jejunum/metabolism , Microsomes, Liver/metabolism , Mixed Function Oxygenases/metabolism , Nomifensine/administration & dosage , Rats , Rats, Inbred StrainsABSTRACT
The pineal gland of the male rat does not appear to rely on prior conversion of testosterone to estradiol for the stimulant effect of testosterone on pineal melatonin and 5-methoxytryptophol synthesis.
Subject(s)
Estradiol/pharmacology , Pineal Gland/metabolism , Serotonin/metabolism , Testosterone/pharmacology , Animals , Castration , Indoles/metabolism , Male , Melatonin/biosynthesis , Organ Culture Techniques , RatsSubject(s)
Indoles/metabolism , Pineal Gland/metabolism , Serotonin/metabolism , Animals , Female , Hydroxyindoleacetic Acid/analogs & derivatives , Hydroxyindoleacetic Acid/metabolism , Hydroxytryptophol/metabolism , Male , Melatonin/metabolism , Organ Culture Techniques , Rats , Rats, Inbred Strains , Serotonin/analogs & derivativesABSTRACT
A new antidepressive drug, S1694, produces increased locomotor activity (LA) in mice, but less so than d-amphetamine. This effect is decreased by pimozide, phenoxybenzamine, as well as by pretreatment of the animals with reserpine or alpha-methyl-p-tyrosine methyl ester (H44/68). S1694 inhibits active dopamine (DA) uptake into rat striatal synaptosomes, but not noradrenaline (NA) uptake into rat hypothalamic synaptosomes, or serotonin (5-HT) uptake into rat midbrain synaptosomes, in the concentrations used. The inhibition of DA uptake appears tp be competitive and the inhibition constant estimated is 1,3 X 10(-6) M. In addition, S1694 releases DA in the same concentrations, and NA as well as 5HT at higher concentrations. It is concluded that S1694 activates LA primarily by inhibitionof DA re-uptake and DA release. The central DA system activation may be important in the antidepressive effect.
