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W J Freed

Publications and source records attributed to W J Freed.

At least 145 records · Page 8Linked to original sources
PubMed1981

Effect of dopamine agonists and antagonists on the electrical activity of substantia nigra neurons transplanted into the lateral ventricle of the rat.

Pieces of fetal rat mesencephalon containing the substantia nigra were transplanted into the lateral ventricle of rats pretreated with 6-OHDA injections into the ipsilateral substantia nigra. Extracellular recordings from these grafts revealed spontaneously active neurons with action potential waveforms and firing rates similar to those found in substantia nigra zona compacta in situ. Furthermore, local application of dopamine agonists inhibited, while dopamine antagonists increased zona compacta activity, both in situ and of cells from nigral grafts. We conclude that substantia nigra grafts contain spontaneously active neurons similar to those of zona compacta in situ, and that some of the mechanisms regulating nigral neuronal activity in situ are also present in this preparation.

Action Potentials↗
PubMed1981

Impairment of instrumental learning in rats by glutamic acid diethyl ester.

Glutamic acid diethyl ester (GDEE), a putative antagonist of glutamate-induced neuronal excitations, was administered prior to an instrumental conditioning task motivated by food reinforcement. A profound impairment of learning was produced in animals receiving 240 or 480 mg/kg of GDEE. Performance was not impaired by GDEE in rats that had previously learned the task. These findings support suggestions that central excitatory processes play an important role in learning phenomena, in particular when these learning phenomena involve acquisition of new behavioral patterns.

Animals↗
PubMed1980

Restoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: long-term behavioral, biochemical, and histochemical studies.

Motor deficits produced in rats by unilateral substantia nigra lesions have been found to be reduced by grafts of fetal rat substantia nigra to the dopamine denervated caudate nucleus. In the present study these grafts were examined behaviorally, histochemically, and biochemically over six to 10-month periods. The grafts were found to survive in a healthy condition and contain catecholaminergic cells and fibers after eight to ten months. Concentrations of dopamine in adjoining parts of the caudate nucleus were increased when examined six months after grafting. Apomorphine induced rotation was reduced by the grafts, and these reductions persisted for at least six months. Although signs of aging were observed in the brains of the host animals when sacrificed eight to ten months after grafting, the grafts remained healthy and showed no signs of aging or deterioration. It is concluded that substantia nigra grafts can become permanent, functional constituents of the brains of host animals with prior substantia nigra lesions.

Animals↗
PubMed1980

Chronic ethanol intake and synaptosomal glutamate binding activity.

The studies presented above add further support to the notion that one of ethanol's most important sites of activity may be the plasma membrane of cells. In addition, they provide an example of how ethanol's effects on these membranes may affect the function of protein molecules associated with nerve cell membranes such as the receptive sites for the putative excitatory neurotransmitter L-glutamic acid. The result of chronic ethanol administration is an apparently enhanced sensitivity to glutamate action in the CNS as measured by either the increases in L-glutamate binding activity or the increased Ca2+ mobilization as a result of glutamate interaction with the synaptosomal membranes. Both of these processes exhibit an enhancement of the maximum response with little or no change in the KD for binding of L-glutamic acid to its receptor site. Finally, it was demonstrated by means of in vivo experiments that there is an apparent sensitization to glutamate during the induction of ethanol dependence, and that this enhanced sensitivity may be causally linked to some of the signs of the post withdrawal CNS hyperexcitability.

Alcoholism↗
PubMed1980

Neuropharmacological studies of phencyclidine (PCP)-induced behavioral stimulation in mice.

A variety of drugs were screened to determine which were capable of blocking the behavioral stimulation produced in mice by acute administration of phencyclidine (PCP). Chlorpromazine and clozapine blocked PCP-induced stimulation, while haloperidol, reserpine, and alpha-methyl-p-tyrosine did not. The GABA receptor agonists imidazole acetic acid and muscimol blocked PCP, but other drugs that influence GABA, such as dipropylacetic acid, baclofen, and diazepam, were ineffective. Yohimbine and methysergide also blocked PCP in high dosages, but other drugs with comparable alpha-noradrenergic and serotonergic blocking properties (phentolamine, cyproheptadine, and cinnanserin) were ineffective. Cholinergic and anticholinergic drugs, beta-noradrenergic and opiate antagonists and nonspecific sedatives and convulsants were also ineffective. These findings suggest that chlorpromazine, clozapine, yohimbine, and methysergide may share a property that is unlike their primary known modes of action on dopaminergic, alpha-noradrenergic, and serotonergic neurotransmitter systems, and that this property accounts for their ability to block PCP. However, the effectiveness of GABA agonists appears to be mediated through direct activation of GABA receptors. It is suggested that chlorpromazine and imidazole acetic acid should be considered as possible drug treatments for PCP toxicity.

Animals↗
PubMed1980

Production of convulsions in mice by the combination of methionine and homocysteine.

Behavioral effects of methionine have been attributed to either increased availability of methyl groups for the production of methylated amines or accumulation of convulsive metabolites. If the second hypothesis is correct, methionine would be expected to have convulsive properties either by itself or in combination with subconvulsive dosages of other known convulsants. Methionine alone did not induce convulsions when administered by various routes in dosages of 250--13,000 mg/kg, although larger doses of methionine (500--4,000 mg/kg) decreased behavioral activity. However, methionine pretreatment (125--1,000 mg/kg) markedly enhanced convulsions in animals challenaed with subconvulsine dosages of homocysteine. Pentylenetetrazol was less effective than homocysteine in promoting convulsions in methionine-pretreated animals. Although the convulsive effects of methionine were not shared by other natural amino acids (glutamate, asparate, cysteine, tryptophan, and others), ethionine enhanced homocysteine-induced convulsions almost as effectively as did methionine. Methionine thus promotes convulsions under certain conditions, plerhaps due to an accumulation of homocysteine or of other metabolites with convulsive properties.U

Animals↗
PubMed1980

Calcitonin reduces feeding in man, monkey and rat.

It is proposed that calcitonin is a hormonal mediator of the satiety reflex. To test this hypothesis, effects of calcitonin on feeding and drinking were measured in rats and in rhesus monkeys. In monkeys, calcitonin produced severe (90%) and prolonged (3-5 days) reduction in feeding, and smaller decreases in drinking. In rats calcitonin decreased feeding in a dose-related manner over 24 hours, but increased drinking and urine output. A modest loss in body weight (2%) was also observed in psychiatric patients given calcitonin. It is suggested that calcitonin reduces feeding either through its effects on calcium metabolism, or by a direct action on the central nervous system.

Animals↗
PubMed1980

The role of cholinergic supersensitivity in the medical symptoms associated with withdrawal of antipsychotic drugs.

From a review of the clinical literature, the authors determined that the medical symptoms of neuroleptic withdrawal occurred more frequently with neuroleptics having potent anticholinergic effects than with those having weak anticholinergic actions. When antiparkinsonian agents were not simultaneously withdrawn, there was a striking difference between these two categories of neuroleptics. Experiments with mice showed that withdrawal of haloperidol, a neuroleptic with weak anticholinergic effects, produced subsensitivity (depression of locomotor activity and seizure thresholds) to the cholinergic effects of physostigmine. These findings support the theory that the medical side effects of neuroleptic withdrawal are due to rebound cholinergic hypersensitivity associated with the anticholinergic actions of these drugs, rather than being related to their dopamine-blocking activity.

Animals↗
PubMed1980

Anomalous behavioral response to imidazoleacetic acid, a GABA agonist, in animals treated chronically with haloperidol.

Short-term haloperidol treatment decreases the stimulant effects of drugs with dopaminelike actions, while withdrawal from long-term haloperidol treatment enhances the effects of such drugs. In the present study, we have shown that withdrawal from long-term haloperidol treatment decreases or eliminates the tendency for imidazole-4-acetic acid, a GABA agonist, to decrease the locomotor activity of mice. Acute haloperidol treatment did not duplicate these effects. It is suggested that chronic administration of haloperidol causes changes in a variety of systems in the brain, and that the GABA system in particular is profoundly altered by such treatment.

Animals↗