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Biomedical subjects

W J Freed

Publications and source records attributed to W J Freed.

At least 109 records · Page 6Linked to original sources
PubMed1987

Diltiazem or verapamil prevents haloperidol-induced apomorphine supersensitivity in mice.

Chronic thioridazine treatment in animals has been reported to produce less dopaminergic supersensitivity than other neuroleptics. This difference may be due to the potent calcium channel inhibitory effect of thioridazine. To test this hypothesis Swiss-Webster mice were treated chronically (28 d) with calcium channel inhibitors (CCI's) - diltiazem, nifedipine or verapamil - with or without haloperidol. Following three days of drug withdrawal, mice were tested for amphetamine-induced locomotion and apomorphine-induced cage climbing. Co-administration of diltiazem or verapamil (but not nifedipine) prevented the development of haloperidol-induced behavioral supersensitivity to apomorphine. Co-administration of CCI's with haloperidol did not affect the development of amphetamine supersensitivity. These data support the hypothesis that co-administration of haloperidol and a CCI (verapamil or diltiazem, but not nifedipine) would mimic the effects of thioridazine treatment alone.

Amphetamine↗
PubMed1987

Normal neuronal cell bodies of the nucleus tractus mesencephalici nervi trigemini react with antibodies against phosphorylated epitopes on neurofilaments.

Reactivity to antibodies directed against phosphorylated neurofilament epitopes is normally present in axons. Phosphorylated neurofilament immunoreactivity is not generally found in neuronal perikarya, except in abnormal states such as Alzheimer's disease. We found that cytoplasm of neurons of the nucleus tractus mesencephalici nervi trigemini in normal mice and rats reacts with monoclonal antibodies against phosphorylated epitopes on neurofilaments. This suggests either that phosphorylated epitopes on neurofilaments are localized in the perikarya of some normal neurons or that the antibodies that were used (SMI 31 and SMI 34) recognize more than phosphorylated epitopes.

Animals↗
PubMed1987

Embryonic substantia nigra grafts innervate embryonic striatal co-grafts in preference to mature host striatum.

Embryonic substantia nigra grafts partially reinnervate the dopamine-denervated corpus striatum when implanted adjacent to that structure. This reinnervation is generally limited to a small portion of the denervated striatum and does not completely compensate for the behavioral effects of a 6-hydroxydopamine lesion of the substantia nigra. This limited reinnervation may be due to the fact that adult denervated striatum is not an ideal target for dopaminergic neurites. To test this hypothesis, embryonic striatum and embryonic substantia nigra were implanted together into the lateral ventricle of adult rats, adjacent to the denervated striatum. Five months after transplantation, fluorescence histochemistry showed that the embryonic striatal grafts were exclusively reinnervated with little or no reinnervation of the adult host striatum. When substantia nigra was implanted without embryonic striatal co-grafts, reinnervation of the host striatum was observed. We conclude that embryonic striatum is a better target tissue than adult denervated striatum for developing dopaminergic neurites and hypothesize that this difference may be due to the presence or the absence of specific trophic factors.

Animals↗
PubMed1987

The dopamine D-2 antagonist, Ro 22-1319, inhibits the persistent behavioral syndrome induced by iminodipropionitrile (IDPN) in mice.

Chronic administration of beta,beta'-iminodipropionitrile causes a persistent syndrome of excitement, choreoathetoid movements, and circling (the "ECC-syndrome") which persists indefinitely after termination of the IDPN injections. Ro 22-1319 is a specific D-2 dopamine receptor antagonist which was recently synthesized to fit a hypothetical model of the D-2 receptor. Ro 22-1319 inhibited several aspects of the ECC-syndrome, although some of its components, such as backward pedaling and forepaw treading reminiscent of the serotonin syndrome, were exacerbated. These results suggest that several neurotransmitter systems may be involved in the ECC-syndrome.

Animals↗
PubMed1987

Anatomical mapping of the rat hypothalamus for calcitonin-induced anorexia.

The primary physiological function of calcitonin, a peptide hormone secreted by the thyroid gland, is to modulate plasma calcium concentrations. Calcitonin also has several effects on the central nervous system including an inhibition of feeding behavior. In the present study synthetic salmon calcitonin (15 ng in 0.3 microliter) was found to produce a marked suppression of eating when infused in several hypothalamic areas. The greatest inhibition was produced by infusions into the paraventricular nucleus of the hypothalamus, the perifornical area and several areas on the floor of the hypothalamus. A less marked inhibition of eating was produced by infusions in the nucleus accumbens. Infusions in the olfactory tubercule, the ventrolateral hypothalamus, the medial forebrain bundle and the posterior nucleus of the hypothalamus had no effect. It is concluded that the anorectic effects of calcitonin on the central nervous system are mediated by several hypothalamic and extrahypothalamic sites.

Animals↗
PubMed1987

Regional localization of the antagonism of amphetamine-induced hyperactivity by intracerebral calcitonin injections.

Calcitonin receptors are found in the brain, and intracerebral infusions of calcitonin can produce behavioral effects. Among these behavioral effects are decreases in food intake and decreases in amphetamine-induced locomotor activity. In previous experiments we found that decreases in food intake were induced by local administration of calcitonin into several hypothalamic sites and into the nucleus accumbens. In the present experiment calcitonin decreased locomotor activity when locally injected into the same sites where it decreases food intake. The areas where calcitonin is most effective in decreasing locomotor activity are located in the hypothalamus and nucleus accumbens, suggesting that these areas are the major sites of action of calcitonin in inhibiting amphetamine-induced locomotor activity.

Animals↗
PubMed1987

Clonidine and prazosin block the iminodipropionitrile (IDPN)-induced spasmodic dyskinetic syndrome in mice.

The effects of drugs with selective action on alpha 1- or alpha 2-adrenoceptors were investigated on persistent head twitches, vertical neck dyskinesia, and the random circling behaviors induced by chronic intraperitoneal injections of IDPN. The alpha agonist clonidine and the alpha antagonist prazosin inhibited the IDPN-induced behavioral syndrome whereas the alpha antagonist yohimbine had no significant effect. These results suggest that dysregulation of a facilitatory noradrenergic input to cortical and/or subcortical motor areas may be involved in the abnormal movements caused by chronic treatment with IDPN.

Animals↗
PubMed1986

Properties of PC12 pheochromocytoma cells transplanted to the adult rat brain.

The possibility of employing PC12 pheochromocytoma cells for transplantation into the rat brain as a substitute for adrenal chromaffin cells was examined. Cultured PC12 cells were implanted into the striatum of rats and examined after one day to 20 weeks by fluorescence histochemistry and immunocytochemical staining for tyrosine hydroxylase and a surface antigen of PC12 cells. Between 800 and 3000 cells survived the implantation procedure and persisted relatively unchanged for about one week. Long-term survival of small numbers of PC12 cells was observed in nine of 14 animals, although the number of surviving cells was reduced after 7.5-20 weeks as compared to earlier time periods. By 14-20 weeks after implantation, most of the remaining cells had developed processes. In other animals, there appeared to have been an initial large increase in the number of cells, followed by complete death of the graft. In many of these animals with no surviving cells, large deposits of hemosiderin were found at the implantation site, an apparent residue of earlier tumor growth. Thus in some animals, the number of PC12 cells apparently increased initially, but in these animals the graft was ultimately rejected. In other animals, small numbers of PC12 cells survived for up to 20 weeks, and many of these cells eventually developed neurite-like processes. Continued uncontrolled tumor growth was not observed.

Adrenal Gland Neoplasms↗
PubMed1986

Inhibition of quisqualate-induced seizures by glutamic acid diethyl ester and anti-epileptic drugs.

Glutamic acid diethyl ester (GDEE) is a glutamate antagonist which acts preferentially at the quisqualate-sensitive receptor and has been shown to be an effective anticonvulsant in alcohol withdrawal and homocysteine-induced seizures but ineffective in other seizure models. To better characterize the role of the quisqualate-sensitive receptor in the generation of seizures, quisqualate was administered to mice by intracerebroventricular (ICV) route and immediate onset generalized seizures were observed. The anticonvulsant properties of GDEE and commonly used antiepileptic drugs (AEDs) were investigated with this seizure model. GDEE given by intraperitoneal blocked quisqualate-induced seizures dose-dependently. Diphenyl-hydantoin (50 mg/kg IP), carbamazepine (50 mg/kg IP), diazepam (1; 4 mg/kg IP), phenobarbital (40; 80 mg/kg IP), and valproic acid (250; 340 mg/kg IP) were also administered prior to quisqualate-seizure induction. Only valproic acid blocked seizures at nonsedating doses. The GABA transaminase inhibitor aminooxyacetic acid (20 mg/kg IP) was ineffective, suggesting that here valproic acid is active at excitatory receptors rather than by potentiating GABA post-synaptic inhibition. These data are consistent with the hypothesis that the quisqualate-sensitive receptor is involved in some forms of clinically observed seizures, particularly those which are controlled by valproic acid.

Aminooxyacetic Acid↗
PubMed1986

Intrastriatal adrenal medulla grafts in rats. Long-term survival and behavioral effects.

Rats with rotational behavior consequent to unilateral lesions of the substantia nigra have been proposed for an experimental model of Parkinson's disease. Adrenal medulla or embryonic substantia nigra grafts in the lateral ventricle of these animals reduce this rotational behavior. For application to primate and human subjects, it may be necessary to implant tissue directly into the parenchyma of the corpus striatum rather than into the ventricle in order to achieve a sufficient distribution of the grafted tissues and increase the efficacy of the grafts. In the present study, the properties of intraparenchymal adrenal medulla grafts were investigated. Grafts were obtained from both young (4 to 5 weeks old) and aging (22 to 24 months old) donor rats. Much of the implanted tissue did not survive, although 200 chromaffin cells per recipient rat were found to have survived for at least 6 months. All of the surviving cells developed process-like cytoplasmic extensions, although these processes did not appear to have reinnervated host brain tissue. Grafts from both young and aging donor rats prevented a slight deterioration in the performance of a sensory neglect test that was observed in a control group that received grafts of sciatic nerve. There was also a tendency that did not reach statistical significance for grafts from young (but not from aging) donors to decrease apomorphine-induced rotational behavior. It is concluded that, although the corpus striatum does not appear to provide a particularly favorable environment for the implantation of adrenal medulla grafts, striatal implants of adrenal medulla might become a promising procedure if a means of improving the survival of these tissues could be developed.

Adrenal Medulla↗
PubMed1985

Promoting functional plasticity in the damaged nervous system.

Damage to the central and peripheral nervous system often produces lasting functional deficits. A major focus of neuroscience research has been to enhance functional restitution of the damaged nervous system and thereby produce recovery of behavioral or physiological processes. Promising procedures include surgical, physical, and chemical manipulations to reduce scar formation and minimize the disruption of support elements, administration of growth-stimulating substances, tissue grafts to bridge gaps in fiber pathways, and embryonic brain tissue grafts to provide new cells with the potential to generate fiber systems. Two elements are required for functional nervous system repair: (i) neurons with the capacity to extend processes must be present, and (ii) the regenerating neurites must find a continuous, unbroken pathway to appropriate targets through a supportive milieu.

Age Factors↗
PubMed1985

Survival of dissociated adrenal chromaffin cells of rat and monkey transplanted into rat brain.

Adrenal chromaffin cells from adult rats and monkeys were mechanically dissociated and implanted into the striatum of adult rats by stereotaxic injection. Rat chromaffin cells survived (5%) and showed differentiation by forming processes 1 h-28 days after implantation. Monkey chromaffin cells survived for 48 h but showed very little formation of processes. The method presented allows rapid nonenzymatic dissociation and transplantation of adrenal medullary cells.

Adrenal Medulla↗
PubMed1985

Effects of betaine on seizures in the rat.

The ability of betaine to block homocysteine, pentylenetetrazol, and electroshock induced seizures in mice has previously been observed. In this study, betaine administered IP and intraventricularly to rats blocked pentylenetetrazol-induced seizures, but IP betaine did not block audiogenic seizures. Intraventricular betaine was about 1000-fold more potent than IP betaine in blocking PTZ-induced seizures. Glycine, a component of the betaine molecule, was ineffective. It is concluded that betaine has an appreciable but selective effect in controlling experimental seizures in rats. This effect is mediated directly by the brain, and is not due to metabolism of betaine to glycine.

Acoustic Stimulation↗
PubMed1985

Prevention of strychnine-induced seizures and death by the N-methylated glycine derivatives betaine, dimethylglycine and sarcosine.

Betaine (N,N,N-trimethylglycine) and N,N-dimethylglycine have been reported to have anticonvulsant properties in animals. The purpose of the present study was to determine whether these compounds can antagonize strychnine-induced seizures when administered intraperitoneally and to compare their effects with those of sarcosine (N-methylglycine) and glycine. Betaine, N,N-dimethylglycine and sarcosine were equipotent in decreasing the incidence of seizures and death, causing a 38 to 72 percent decrease in the incidence of seizures and death at a dosage of 5 mmole/kg. Glycine had no effect. Thus anticonvulsant activity is conferred to glycine by a single N-methylation.

Animals↗