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Biomedical subjects

B Lerer

Publications and source records attributed to B Lerer.

At least 199 records · Page 11Linked to original sources
PubMed1984

Electroconvulsive shock and brain muscarinic receptors: relationship to anterograde amnesia.

Rats were administered one electroconvulsive shock daily for 7 days (ECS X 7) and were killed 24 hours after the last treatment. Muscarinic cholinergic receptor number, as determined by [3H] quinuclidinyl benzilate [( 3H]QNB) binding, was significantly reduced in the cerebral cortex. A parallel group of rats was trained on a passive avoidance task 24 hours following the last ECS and tested for retention of the original avoidance response 24 hours later; these animals exhibited a profound amnesia. Animals tested 1 hour following training were not amnestic, indicating that learning was unimpaired. Animals trained 7 days following ECS X 7 were not amnestic and [3H] QNB binding changes were not demonstrable at this time. A single ECS which does not significantly affect cortical [3H] QNB binding, did not induce amnesia in rats trained 24 hours after the treatment and tested 24 hours later. The parallel, cumulative nature of ECS-induced muscarinic receptor down-regulation and ECS-induced anterograde amnesia suggests a possible causative relationship.

Amnesia↗
PubMed1984

Carbamazepine and haloperidol v placebo and haloperidol in excited psychoses. A controlled study.

Carbamazepine has recently been reported to have therapeutic potential in mania. We studied carbamazepine plus haloperidol v placebo plus haloperidol in excited psychoses in a controlled double-blind design. Twenty-three patients completed five weeks of carbamazepine-haloperidol therapy, and 20 patients placebo-haloperidol therapy. Brief Psychiatric Rating Scale ratings showed superior improvement in the group receiving carbamazepine plus haloperidol. This benefit was as apparent in excited schizophrenia as in mania. No unusual toxicity was observed because of the combination of haloperidol with carbamazepine.

Adult↗
PubMed1984

Effect of cyclo(Leu-Gly) on reserpine-induced hypomotility and increases in cortical beta-adrenergic receptors.

Previous studies have indicated that the endogenous peptide, melanotropin release inhibiting factor (MIF) and its analog cyclo(Leu-Gly) ( CLG ) facilitate dopamine (DA) receptor agonist binding and inhibit DA receptor supersensitivity induced by neuroleptics and opiates. The effect of CLG was tested on beta-adrenergic hypersensitivity induced by reserpine to ascertain whether CLG has effects on other neuronal systems besides DA. Administration of reserpine to rats induced hypomotility and enhanced binding of [3H]dihydroalprenolol (DHA) to cortical membranes. Concurrent administration of CLG blocked both the hypomotility and the enhanced [3H]DHA binding to cortical membranes. Lithium has also been shown to prevent reserpine induced hypomotility and increased cortical [3H]DHA binding. These studies suggest that CLG may be producing its effect either like lithium or by an amphetamine like action. If CLG can be shown to have lithium like activity, it could prove to be useful in the treatment of mania.

Animals↗
PubMed1984

Enhancement of memory by a cholinesterase inhibitor associated with muscarinic receptor down-regulation.

Rats trained on a passive avoidance task 24 hours following a single intraperitoneal injection of diisopropyl fluorophosphate (DFP, 1.2 mg/kg) showed enhanced retention when tested 7 days later. In a parallel group of rats, reduced cortical [3H] quinuclidinyl benzilate binding was demonstrable 24 hours following DFP administration. The association of reduced muscarinic receptor binding and enhanced performance on a memory task contradicts previous reports which suggested that retention was impaired by treatments which down-regulate muscarinic receptors. This contradiction may be reconciled if pre-synaptic factors such as agonist availability are considered in conjunction with post-synaptic receptor effects.

Analysis of Variance↗
PubMed1984

Effect of treatment and withdrawal from chronic lithium in rats on stimulant-induced responses.

Chronic lithium (Li) administration to rats was found to inhibit the hyperactivity induced by 0.5 mg/kg d-amphetamine but not that induced by 1.0 mg/kg d-amphetamine. Contradictory results on the ability of Li to inhibit amphetamine-induced hyperactivity may be due to the different dosages of amphetamine employed. 2 days after withdrawal from 3 weeks of chronic Li administration, rats showed no rebound supersensitivity of the hyperactivity response to 0.5 mg/kg d-amphetamine. Surprisingly, Li-withdrawn rats showed a marked subsensitivity of the stereotypy response to apomorphine. Such subsensitivity to apomorphine in Li withdrawal may relate to recent reports of homovanillic acid increases in rat brain in Li withdrawal, and to clinical reports of Li withdrawal inducing psychosis.

Animals↗
PubMed1984

Electroconvulsive shock and neurotransmitter receptors: implications for mechanism of action and adverse effects of electroconvulsive therapy.

Neurochemical effects of electroconvulsive shock (ECS) in three neurotransmitter-receptor systems were studied in relation to the mechanism of action and adverse effects of ECT. In the noradrenergic system, chronically administered ECS, along with other effective antidepressant treatments, has been consistently reported to down-regulate beta-adrenergic receptors in rat cerebral cortex. Even when ECS was administered according to an intermittent clinically equivalent schedule, a 21% reduction in cortical 3H-DHA binding to beta-adrenoreceptors could be demonstrated 4 days after the last treatment. However, the role of presynaptic NA events in beta-adrenoreceptor down-regulation by ECS and the antidepressant mechanism of ECT remains to be clarified. Compared to the MAO inhibitor clorgyline, repeated ECS pretreatment induced only a moderate increase in NA release from a rat cortical vesicular preparation and minimally reduced the sensitivity of the preparation to release-inhibition by clonidine. In the dopaminergic system, a clinically equivalent ECS schedule had no direct effect on behavioral or biochemical indices of DA receptor sensitivity. However, the same ECS schedule significantly attenuated haloperidol-induced behaviorally and biochemically measured DA supersensitivity in the same model in which parallel effects had been reported for lithium. The possibility that a "receptor-stabilizing" mechanism may be common to ECT and lithium is considered on the basis of similarities in the clinical profiles of the two treatments. In the cholinergic system, repeated ECS significantly reduced 3H-QNB binding to muscarinic cholinergic receptors in rat cerebral cortex and hippocampus. Concurrently administered ECS also blocked the increase in 3H-QNB binding caused by chronic atropine administration. ECS effects on muscarinic cholinergic receptors may have relevance to the antidepressant mechanism of ECT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

The effect of repeated electroconvulsive shock treatment and chronic lithium feeding on the release of norepinephrine from rat cortical vesicular preparations.

The effect of repeated electroconvulsive shock (ECS) treatment and chronic LiCl feeding on calcium-dependent, K+-evoked release of [3H] norepinephrine from rat cortical vesicular preparation was studied. There was no significant effect of either acute or repeated ECS treatment on [3H]norepinephrine release in cortical vesicles obtained from animals treated for either 1 or 10 days. Release of norepinephrine was examined over a range of CaCl2 concentrations. Clonidine effectively inhibited release of [3H]norepinephrine in cortical vesicles obtained from control and ECS-treated animals. K+-evoked release of [3H]norepinephrine at low (0.2 mM) and high (1.0 mM) CaCl2 concentrations was significantly increased in cortical vesicles obtained from LiCl-treated animals. Clonidine effectively inhibited release of [3H]norepinephrine in cortical vesicles obtained from both control and LiCl-fed animals. These results suggest a possible common mechanism of action of antidepressant drug therapy on presynaptic release of norepinephrine from nerve terminals.

Animals↗
PubMed1983

Loss of cholinergic neurons in the rat neocortex produces deficits in passive avoidance learning.

Bilateral kainic acid lesions of the ventral globus pallidus produced a significant and selective cortical decrease in choline acetyltransferase activity in the rat brain. When lesioned and control subjects were compared on performance of a step-through passive avoidance task, lesioned rats showed a marked retention deficit 24 hr after the initial training trial. This experimentally-induced memory deficit associated with a cortical cholinergic neuronal loss resembles the deficits in senile dementia of the Alzheimer type and may provide a useful animal model for studying the disease.

Acetylcholine↗
PubMed1983

Clinical implications of research on the mechanism of action of lithium.

Lithium is a unique drug in its clinical profile in psychiatry. Lithium has numerous biochemical effects, but none has yet been proven to be its mode of therapeutic action. Inhibition of noradrenaline-sensitive adenylate cyclase is reviewed as the only biochemical effect of lithium shown to occur in both animals and man at therapeutic lithium concentrations. A tetracycline antibiotic, demeclocycline, also blocks noradrenaline-sensitive adenylate cyclase. A clinical trial of demeclocycline in mania would provide a test of the adenylate cyclase theory of lithium action.

Adenylyl Cyclase Inhibitors↗
PubMed1983

Clinical strategies for evaluating ECT mechanisms--pharmacological, biochemical and psychophysiological approaches.

Although ECT is a highly effective treatment for severe depression and other psychiatric syndromes, its mode of action is not known. Recent studies have suggested that effects of ECT on central neurotransmitter receptors may underlie its therapeutic action. The effects of chronically administered electroconvulsive shock on receptors for dopamine, serotonin, noradrenaline, acetylcholine and endorphins in rodent brain, are reviewed. Strategies for evaluating the relevance of these animal findings to mechanisms of action of ECT in humans are discussed.

Animals↗
PubMed1983

Effect of electroconvulsive shock on muscarinic cholinergic receptors in rat cerebral cortex and hippocampus.

Single electroconvulsive shock (ECS) induced no change in [3H]quinuclidinyl benzilate ([3H]QNB) binding to muscarinic cholinergic receptors in rat cortex and hippocampus. ECS administered once daily for 7 days induced a significant reduction in [3H]QNB binding in both brain areas. Concurrent ECS reversed the significant increase in cortical [3H]QNB binding induced by chronic atropine administration. These findings may have relevance to the antidepressant or amnestic effects of electroconvulsive therapy.

Animals↗
PubMed1982

Lithium does not prevent ECS-induced decreases in beta-adrenergic receptors.

Electroconvulsive shock (ECS) reduces the number of rat cortical beta-adrenergic receptors. Lithium has been reported in several systems to prevent receptor changes induced by other agents. However, the present experiment reports that chronic lithium does not prevent the reduction in dihydroalprenolol binding induced by ten daily ECS treatments.

Animals↗
PubMed1982

The effect of chronic bromocriptine and L-dopa on spiperone binding and apomorphine-induced stereotypy.

Chronic treatment with dopamine (DA) agonists has been reported in various paradigms to cause supersensitivity of DA receptors or, contradictorily, subsensitivity of DA receptors. The present study administered 15 mg/kg bromocriptine for 7 days and measured both striatal spiperone binding and apomorphine (AP)-induced stereotypy. A significant decrease in AP-induced stereotypies was observed after chronic bromocriptine treatment, but without a significant parallel decrease in striatal spiperone binding. These results probably do not represent a true agonist-induced subsensitivity, but possibly show that residual bromocriptine in vivo may antagonize AP-induced stereotypy. Since some reports have suggested that L-Dopa may specifically reverse the increases in DA receptor number induced by chronic haloperidol, we also studied the effect of 7 days of L-Dopa treatment after 6-week chronic haloperidol treatment of mice. While chronic haloperidol significantly increased striatal spiperone binding, subsequent L-Dopa treatment did not reverse this biochemical supersensitivity. It is concluded that agonist induction of subsensitivity in the DA system is difficult to reproduce and may depend on highly specific dosage conditions and treatment schedules.

Animals↗
PubMed1982

Lithium does not prevent agonist-induced subsensitivity of human adenylate cyclase.

In a previous study 11 depressed patients were treated with salbutamol, a beta-2 adrenergic agonist, and beta-2 adrenergic receptor sensitivity was evaluated by measuring the plasma cyclic AMP rise after an iv dose of salbutamol. Salbutamol treatment induced subsensitivity of the beta-adrenergic adenylate cyclase with a time course paralleling the antidepressant effects. In the present study nine patients who were depressed despite treatment with lithium were treated with salbutamol plus lithium. Subsensitivity of the beta-adrenergic adenylate cyclase developed in the presence of lithium to the same degree as in patients treated with salbutamol alone. These results represent the first human study of the theory that lithium stabilizes receptor sensitivity changes. Lithium's failure to prevent subsensitivity agrees with reports that lithium fails to prevent impramine-induced subsensitivity of beta-adrenergic receptors in rat cortex. Lithium stabilization of receptor sensitivity of beta-adrenergic receptors in rat cortex. Lithium stabilization of receptor sensitivity would therefore appear to be unidirectional, preventing supersensitivity but not subsensitivity.

Adenylyl Cyclases↗