Psychomotor stimulant vs. local anesthetic effects of cocaine: role of behavioral sensitization and kindling.
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Anesthetics, Local↗
Biomedical subjects
S R Weiss
Publications and source records attributed to S R Weiss.
Expression of MHC class I genes in mouse hepatitis virus (MHV-A59) infection and in multiple sclerosis.
Our studies revealed that virus induced demyelination as well as human inflammatory demyelination involves upregulation of class I MHC genes and surface expression of antigens encoded by these genes. Induction involves the action of an intermediate soluble factor/s which is at present unknown. These findings suggest that MHC class I restricted, cytotoxic T lymphocyte (CTL) reactions, against self or foreign antigens may play a role in these conditions. These findings may help to elucidate the mechanism of coronavirus-induced demyelination as well as the pathogenesis of multiple sclerosis.
Animals↗
Lack of effect of chronic carbamazepine on brain somatostatin in the rat.
We investigated the effects of chronic carbamazepine treatment in rats on brain somatostatin. Following 12 days of carbamazepine treatment, no changes in somatostatin levels were found in any of the brain areas examined which included: amygdala, hippocampus, caudate-putamen, median eminence, arcuate nucleus, nucleus accumbens, nucleus interstitialis of the stria terminalis, nucleus periventricularis, parietal cortex, and occipital cortex. Thus, carbamazepine in low doses does not affect basal levels of brain somatostatin in the rat, in contrast to the previous reports of decreased somatostatin in the cerebrospinal fluid of affectively ill patients.
Animals↗
In vitro synthesis of two polypeptides from a nonstructural gene of coronavirus mouse hepatitis virus strain A59.
The complete nucleotide sequence of nonstructural gene 5 of coronavirus mouse hepatitis virus (MHV) strain A59 has been determined. This sequence contains two potential open reading frames which overlap by five nucleotides. The putative protein products predicted from the sequence are a basic 13,000-Da polypeptide and a 9600-Da polypeptide containing an unusually long hydrophobic amino terminus. RNAs transcribed in vitro from DNAs containing each of the open reading frames in pGEM vectors direct the synthesis in vitro of polypeptides of the sizes predicted by the sequence. An RNA transcript containing both of the open reading frames directs the synthesis primarily of the polypeptide corresponding to the downstream open reading frame. These data suggest that MHV-A59 messenger RNA 5 potentially encodes two proteins and may be preferentially translated from an internal AUG initiation codon.
Amino Acid Sequence↗
Coronavirus mouse hepatitis virus (MHV)-A59 causes a persistent, productive infection in primary glial cell cultures.
MHV-A59 causes a chronic demyelinating disease in mice which is accompanied by persistence of viral genome in white matter. As part of the investigation into the mechanism of viral persistence, infection of glial cells, probable targets for chronic infection, was studied by the use of mixed glial, enriched oligodendrocyte and enriched astrocyte cultures. Following MHV-A59 infection in vitro, approximately 10% of oligodendrocytes and 30% of astrocytes expressed viral antigens in the absence of overt cytopathic effect. All cultures released infectious virus for the lifetime of the cultures, for at least 45 days in the case of mixed glial cultures. Cultures derived from previously infected mice were similar to those infected in vitro with respect to percentage of cells expressing viral antigen and levels of infectious virus produced. These results show (1) that glial cells are early sites of infection in vivo as well as sites of infection in vitro cultures, and (2) that glial cells support a non-lytic but productive infection in vitro and thus may contribute to viral persistence in vivo.
Animals↗
Carbamazepine and carbamazepine-10,11-epoxide inhibit amygdala-kindled seizures in the rat but do not block their development.
The effect of carbamazepine and its -10,11-epoxide on the development of amygdala-kindled seizures and on completed kindled seizures in the rat was evaluated. Neither carbamazepine (15 mg/kg) nor the -10,11-epoxide (15 mg/kg) was capable of preventing the development of amygdala-kindled seizures, although both drugs, at these doses, exerted marked anticonvulsant effects on completed kindled seizures. These data suggest that different phases of kindling are differentially responsive to pharmacological intervention. They also support the conclusion that different mechanisms underlie the acquisition and maintenance of kindled seizures.
Amygdala↗
Persistent upregulation of brain adenosine receptors in response to chronic carbamazepine treatment.
Chronic carbamazepine treatment for a period of 2 weeks caused a highly significant increase in brain adenosine receptors in the rat. The carbamazepine was administered in food pellets in a diet that achieved clinically relevant total plasma concentrations of carbamazepine and its active-10,11-epoxide metabolite. Of the several brain areas examined, the cerebral cortex and hippocampus exhibited the most robust increases in [3H]cyclohexyladenosine (CHA) binding. Increases of 35-40% were observed in these brain regions whereas an 8-10% increase was seen in the cerebellum. The carbamazepine induced increase in brain adenosine receptors in all these areas persisted unabated at 1 and 5 days as well as 2, 4, and 8 weeks following termination of carbamazepine treatment, suggesting a relatively permanent alteration of the adenosine receptor by this drug.
Adenosine↗
The role of context and conditioning in behavioral sensitization to cocaine.
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Animals↗
Coronavirus infection induces H-2 antigen expression on oligodendrocytes and astrocytes.
Infection of the central nervous system by mouse hepatitis virus strain A59, a murine neurotropic coronavirus, induces class I major histocompatibility complex antigens on mouse oligodendrocytes and astrocytes, cells that do not normally express these antigens on their surfaces. This induction, which occurs through soluble factors elaborated by infected glial cells, potentially allows immunocytes to interact with the glial cells and may play a critical role in the pathogenesis of virus-induced, immune-mediated demyelination in the central nervous system.
Animals↗
CRF-induced seizures and behavior: interaction with amygdala kindling.
Intracerebroventricular (i.c.v.) administration of ovine corticotropin-releasing factor (CRF) in doses varying from 10 to 100 micrograms has been reported to produce the late onset of seizures that resemble those observed during electrical kindling of the amygdala. We assessed the effects of repeated CRF administration on seizure development and on subsequent electrical kindling of the amygdala. Rats were administered vehicle or CRF (100 micrograms in 10 microliter of sterile water, i.c.v.) once daily for 5 consecutive days and were rated for seizures and aggressive behavior. On days 1 or 2, all animals receiving CRF developed major motor seizures of late onset (1-5 h post-injection), accompanied by spiking in the amygdala. By day 5, however, no rats had seizures, suggesting the development of tolerance. Defensive biting attacks were also observed following latencies of several hours and tolerance appeared to develop to these as well. After the CRF regimen, treated rats developed amygdala-kindled seizures following electrical stimulation approximately twice as fast as vehicle-injected controls (P less than 0.03). In a second experiment, rats were electrically kindled or sham-kindled prior to receiving i.c.v. CRF (100 micrograms). Kindled animals were significantly less sensitive to the seizure-inducing effects of CRF (P less than 0.03), but were more intensely aggressive than sham-kindled animals or naive rats receiving CRF for the first time.
Amygdala↗
Size-threshold changes after lesions of the visual telencephalon in pigeons.
Fifteen pigeons were tested in a psychophysical procedure that determined the limits of their ability to detect differences in the sizes of stimuli. The results indicated that intact pigeons can reliably discriminate an annulus 3.0 mm in diameter from one that is 3.9 mm in diameter. In the first experiment, pigeons with lesions of the ectostriatum that spared the medial 15% were unimpaired in their size-discrimination ability. Those cases in which the lesions involved both the medial and lateral regions of the ectostriatum were greatly impaired. In a second experiment, these findings were replicated. In some cases, the electrode trajectory was varied to rule out possible effects from non-ectostriatal structures. In addition, the second study indicated that destruction of the medial ectostriatum with the lateral regions intact had no measurable effect on size-difference thresholds. The medial region of ectostriatum is part of the termination field of a second tectofugal pathway to the telencephalon. This pathway passes from the optic tectum to nucleus dorsolateralis posterior thalami and then to the neostriatum intermedium, including the medial ectostriatum. An examination of the data of the present experiment and those of other behavioral studies of the ectostriatum suggest that the medial ectostriatum may be involved in the processing of visual information with low spatial-frequency components and the lateral ectostriatum may be processing information about the high-frequency composition of stimuli.
Animals↗
Electroconvulsive therapy as an anticonvulsant. Implications for its mechanism of action in affective illness.
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Amygdala↗
Discrimination of mirror-image stimuli after lesions of the visual system in pigeons.
Nine pigeons were trained to perform a simultaneous discrimination task with stimuli that were lateral mirror images, vertical mirror images and nonmirror images. All subjects acquired the discriminations rapidly and at approximately equal rates. Following training, bilateral stereotaxic lesions were made in either the visual wulst or ectostriatum, which are telencephalic components of the thalamofugal and tectofugal visual pathways, respectively. After surgery both groups were retrained to their preoperative performance levels or for a maximum of 140 sessions. The performance of the four subjects that received visual wulst lesions was only mildly and transiently impaired and was equally disrupted on each pattern discrimination. The performance of the five subjects that received ectostriatal lesions, however, was markedly and persistently impaired on all pattern discriminations. The impairment was most severe and sustained on the lateral mirror-image discrimination problem in all subjects. Only three of the five subjects with ectostriatal lesions reached their preoperative performance levels on the lateral mirror-image problem, whereas all subjects returned to their preoperative performance levels on the other problems. Possible reasons for this selective deficit in lateral mirror-image pattern discrimination are discussed in relation to interhemispheric pathways and the relative importance of the thalamofugal and tectofugal visual pathways in birds and in mammals.
Animals↗
Relationship of mood alterations to bingeing behaviour in bulimia.
Twelve women with bulimia participated in a study in which they binged and vomited on the day after hospital admission. Caloric intake, time spent bingeing and vomiting, and self-reported mood ratings demonstrated much variation from subject to subject. Both subjective and objective ratings of mood indicated that anxiety decreased more frequently and to a greater extent than depression, both during and after bingeing and vomiting. The present data, obtained in a controlled setting, tend to confirm previous information on binge episodes obtained by self-report from bulimic patients. Bingeing and vomiting episodes may provide bulimic patients with a physiological mechanism for temporarily relieving a dysphoric mood state.
Adult↗
The organ tropism of mouse hepatitis virus A59 in mice is dependent on dose and route of inoculation.
The organ tropism of MHV-A59, a murine coronavirus, was studied in 4-6 week-old C57BL/6 mice inoculated by different routes and with various amounts of virus. MHV-A59 caused hepatitis after intracerebral and intraperitoneal inoculation (two clearly artificial routes) and also after intranasal and intragastric inoculation (two routes more likely to mimic naturally acquired infection). For each route, the severity of hepatitis was dependent on the amount of virus inoculated. Significantly higher doses were needed to cause hepatitis by the intranasal or intragastric routes. We have shown previously that mice inoculated intracerebrally with MHV-A59 develop mild meningoencephalitis followed by chronic central nervous system (CNS) disease, characterized by primary demyelination (1). We extend these results here to show that acute CNS disease can be produced also by intranasal and intragastric inoculation, although much larger doses are needed as compared to intracerebral inoculation. Thus induction of demyelination, not only by the intracerebral route but also by the intranasal route, provides a useful model system to study virus-induced demyelination.
Administration, Intranasal↗
Infection of the basal ganglia by a murine coronavirus.
The coronavirus, mouse hepatitis virus strain A59 (MHV-A59), causes mild encephalitis and chronic demyelination. Immunohistochemical techniques showed that MHV-A59-infected C57BL/6 mice contained dense deposits of viral antigen in the subthalamic nucleus and substantia nigra, with fewer signs of infection in other regions of the brain. The animals showed extra- and intracellular vacuolation, neuronal loss, and gliosis in the subthalamic-nigral region. Such localization is unprecedented among known viral encephalitides of humans and other species. This infection by a member of a viral class capable of causing both encephalitis and persistent infection in several species may be related to postencephalitic parkinsonism.
Animals↗
Differential mediation of the anticonvulsant effects of carbamazepine and diazepam.
Possible mechanisms of action of carbamazepine and diazepam on amygdala-kindled seizures were studied using compounds acting at the central and "peripheral-type" benzodiazepine binding sites. Ro-15-1788, a selective antagonist at the central benzodiazepine site, blocked the anticonvulsant effect of diazepam, but not of carbamazepine. In contrast, Ro5-4864, which acts at the "peripheral-type" benzodiazepine site, blocked the anticonvulsant effect of carbamazepine, but not of diazepam. The effect of Ro5-4864 was itself reversed by PK-11195, a compound that displaces Ro5-4864 binding in vitro and in vivo. These data indicate that the anticonvulsant effects of carbamazepine and diazepam on amygdala-kindled seizures are differentially mediated and suggest that the "peripheral-type" benzodiazepine binding site is functionally involved in the anticonvulsant effect of carbamazepine.
Amygdala↗
Adenosine antagonists. Lack of effect on the inhibition of kindled seizures in rats by carbamazepine.
This study investigates the ability of adenosine antagonists to reverse the anticonvulsant effects of carbamazepine on amygdala-kindled seizures in order to elucidate the possible physiological relevance of the potent effects of carbamazepine on adenosine receptors. At large but subconvulsant doses, neither caffeine nor theophylline altered the anticonvulsant potency of carbamazepine, even though caffeine by itself significantly increased the duration of the kindled afterdischarge. The adenosine agonist cyclohexyladenosine (CHA), administered intraperitoneally at a dose that produced sedation, had no effect on the kindled seizures. Although carbamazepine potently displaces the binding of several adenosine ligands in vitro, the present data do not suggest that the anticonvulsant effects of carbamazepine on amygdalakindled seizures are mediated by an adenosine agonist-like action.
Adenosine↗