Search PubMed⌕ Search

Biomedical subjects

I Hanin

Publications and source records attributed to I Hanin.

At least 145 records · Page 8Linked to original sources
PubMed1978

Effects of chronic lead exposure on levels of acetylcholine and choline and on acetylcholine turnover rate in rat brain areas in vivo.

Rats were exposed to lead acetate from birth, and were killed at the age of 44--51 days for analysis of levels and turnover rates of acetylcholine (ACh). Steady-state levels of ACh were not altered in midbrain, cortex, hippocampus, or striatum of lead-exposed rats. Similarly, no changes in choline (Ch) concentrations were found in cortex, hippocampus, or striatum. In the midbrain, however, a 30% reduction in Ch levels was observed. Changes in specific activity of Ch and ACh were measured as a function of time in selected brain areas of rats infused with a radio-labeled precursor of Ch. Specific activities of ACh were not altered. Ch specific activities were, however, significantly elevated in all brain areas examined, as compared with age-matched control rats. The in vivo ACh turnover rate in cortex, hippocampus, and striatum was diminished by 35%, 54%, 51%, and 33%, respectively. These findings provide direct evidence for an inhibitory effect of lead exposure from birth on central cholinergic function in vivo. Since a significant reduction of body weight was found in those animals treated with lead acetate, the alteration of central cholinergic function may partially be attributed to malnutrition observed in the lead-exposed animals.

Acetylcholine↗
PubMed1978

Central neurotransmitter function and its behavioral correlates in man.

The past decade has witnessed a tremendous increase in knowledge towards understanding the function of various brain neurotransmitter substances in behavior. Experimental observations in animals, utilizing specific pharmacological agents, have enabled the development of certain hypotheses regarding neurochemical substrates of behavior. These have led to cautious applications of complementary studies in humans. As a result, several neurotransmitter-related hypotheses have been developed for the explanation of normal behaviour, as well as of various abnormal behavior states in psychiatry and neurology. These hypotheses are currently undergoing extensive investigation. Highlights of the above sequence of events are presented, in order to provide as general, yet extensive, an overview of the subject as possible. Examples are provided from both basic laboratory investigations and from clinical findings. Principles of brain neurotransmitter function and interactions are reviewed. Various neurotransmitter-related hypothese of psychiatric and neurologic interest are introduced. Finally, the role that toxicants may have on behavior via alteration of brain neurotransmitter function is discussed, using the lead intoxicated animals as an illustrative example.

Animals↗
PubMed1978

The effect of neuroleptics on acetylcholine concentration and choline uptake in striatum: Implications for regulation of acetylcholine metabolism.

It has previously been shown that neuroleptic drugs block an apparently inhibitory influence of dopamine on cholinergic interneurons in striatum, thereby increasing acetylcholine turnover. In this study, systemic administration of the neuroleptic, fluphenazine, decreased the acetylcholine content in the striatum but not the neocortex of rats killed by focussed microwave irradiation. The effect was observed with doses of fluphenazine as low as 0.05 mg/kg, and was also seen after two other neuroleptics, spiroperidol (1 mg/kg) and haloperidol (4 mg/kg). In contrast, neither fluphenazine nor haloperidol pretreatment had any effect on the high affinity accumulation of choline by striatal synaptosomes. These observations suggest that after administration of dopamine receptor antagonists the release and metabolism of acetylcholine in the striatum is increased, but that a compensatory increase in choline uptake does not occur, thereby resulting in a temporary decrease in acetylcholine concentration. On the basis of these findings, we conclude that acetylcholine synthesis is regulated differently in the striatum than in other brain regions.

Acetylcholine↗
PubMed1977

Involvement of both cholinergic and catecholaminergic pathways in the central action of methylphenidate: a study utilizing lead-exposed rats.

The effects of methylphenidate (MPH) and the cholinergic agonists nicotine and oxotremorine were tested on the spontaneous multiple unit activity in the mesencephalic reticular formation of two groups of rats. In control rats i.v. MPH (1 mg/kg), nicotine (0.125 mg/kg), and oxotremorine (0.5 mg/kg) all attenuated the unit activity with latencies of less than 10 min. In another group of rats, exposed to lead acetate since birth, the extent of attenuation of unit activity induced by MPH and nicotine was reduced and the latency of effect was delayed by 45--50 min. The latency of the oxotremorine effect was not changed but the attenuation of unit activity was more pronounced in the lead-treated group. Pretreatment with spiroperidol, to inhibit the aminergic receptors, diminished the inhibitory effect of MPH in the control group but not in the lead-treated group, whereas the attenuating effect of oxotremorine was not affected in either group. These data support our previous evidence that MPH exerts its action in the central nervous system by a cholinergic pathway in addition to published catecholaminergic pathways. Furthermore, the present findings indicate that chronic lead-exposure in rats results in cholinergic hypofunction and supersensitivity at central cholinergic receptor sites. This alteration of central cholinergic function may be partially attributed to the malnutrition observed in the lead-exposed animals.

Animals↗
PubMed1977

Adjustment of lithium dose during lithium-chlorothiazide therapy.

There has been a long-held belief that lithium salts cannot be used in the presence of thiazide diuretics. Recently, however, thiazides have been demonstrated to be not only safe, but actually indicated in two situations in which lithium salts are used. The first is in the treatment of lithium-induced nephrogenic diabetes insipidus and the second is in severe manic depressive illness in which high doses of lithium do not produce therapeutic serum or intraeythrocytic lithium concentrations. This new information now makes it possible for some manic depressive patients with serious medical illnesses (such as hypertension or congestive heart failure), in whom thiazide diuretics are routinely used, to be treated cautiously with lithium carbonate. This paper analyzes data from 13 patients taking lithium carbonate and varying doses of chlorothiazide in order to indicate the approximate magnitude of downward adjustment of daily lithium dose which the clinician must make to safely give 500, 750, and 1,000 mg/day of chlorothiazide.

Chlorothiazide↗
PubMed1977

Amitriptyline plasma levels and clinical response in primary depression.

Sixteen patients with primary depression were treated for 4 wk with amitriptyline. After clinical diagnoses were determined, patients entered a double-blind protocol (amitriptyline or placebo) and their clinical status was determined with the Hamilton Depression Rating Scale by raters blind to the drug type, its dosage and plasma levels. Amitriptyline (AT) and nortriptyline (NT) plasma levels were assayed twice weekly by gas chromatography-mass spectrometry. In the 16 patients, a negative correlation between the Hamilton Score and the mean total tricyclic level (p less than 0.01), as well as with individual plasma levels, was found at the end of the treatment period. When the group was divided into clinical responders and nonresponders, the mean total tricyclic (AT + NT) levels discriminated the two groups by day 12 (p less than 0.001) as well as at the end of the protocol (day 26, 88% of the patients were classified correctly if an arbitrary level of 200 ng/ml total tricyclic plasma level was chosen). These results strongly suggest the presence of a positive correlation between plasma levels and clinical improvement in patients with primary depression.

Adult↗
PubMed1977

Is 2-dimethylaminoethanol (deanol) indeed a precursor of brain acetylcholine? A gas chromatographic evaluation.

Acute administration of deanol-p-acetamidobenzoate (Deaner; deanol) has been reported to elevate brain choline (CH) and acetylcholine (ACh) levels. We have developed a specific and sensitive gas chromatographic assay to measure deanol levels in tissue and have applied this assay to our studies of the effect of acute deanol administration on deanol, ACh and Ch levels in rodent brains. Details of the method are described in this text. This procedure is quantitative and yields reproducible results over a wide range of deanol concentrations (0.30-200 nmol). Seven endogenous and pharmacological parameters have been studied using this procedure. In control rodent brain, liver, heart, lung and plasma, we detected no free endogenous deanol (less than 1 nmol/g). After deanol administration, we were able to detect deanol in tissue and have attempted to determine a relationship between these levels and values of ACh in the same tissue. Regardless of deanol pretreatment time (1-30 minutes) or doses (33.3-3000 mg/kg i.p.) used, we detected no increase in mouse whole brain ACh levels. Likewise, there was no detectable elevation in ACh levels in rat whole brain, cortex, striatum or hippocampus after a 15-minute pretreatment with 550 mg/kg of deanol (i.p.). The only elevation in ACh levels which we detected occurred selectively in the striatum of mice pretreated with a massive dose (900 mg/kg i.p.) of deanol for 30 minutes. This selective increase in striatal ACh levels oculd not, however, be related to levels of deanol in the striatum because there was no greater accumulation of deanol in the striatum than in other brain areas tested or in whole brain. These data do not confirm the results of other investigators who reported elevations in whole brain or striatal ACh levels after acute administration of lower doses of deanol. The data emphasize the need for further investigation into the mode of action of deanol and question its suggested role as an immediate precursor of ACh synthesis in the central nervous system.

Acetylcholine↗