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Biomedical subjects

R B Rosse

Publications and source records attributed to R B Rosse.

At least 19 recordsLinked to original sources
PubMed1999

Stress and a glycinergic intervention interact in the modulation of MK-801-elicited mouse popping behavior.

The ability of D-cycloserine, a partial glycine agonist, to modulate mouse popping behavior elicited by MK-801, a noncompetitive NMDA receptor antagonist, was studied in unstressed and stressed mice. In unstressed animals, D-cycloserine (5.6 and 10 mg/kg) attenuated the ability of MK-801 (1.0 mg/kg) to elicit this behavior. However, the ability of D-cycloserine to attenuate MK-801-elicited mouse-popping behavior was not evident in stressed mice, 24 h after they were forced to swim for up to 10 min in cold water. Thus, the therapeutic value of glycinergic interventions may be limited by environmental factors, such as stress.

Animals↗
PubMed1999

Visual scanning of facial expressions in schizophrenia.

The authors previously observed that schizophrenic patients generated fewer fixations of < or = 50.1 ms in response to faces than did a clinical control group. This study examined whether deficits in short-duration eye movements were related to patients' problems in gestalt perception of faces. Faces were presented in upright and inverted orientations to examine the effects of distorting facial gestalts on eye movements. Normal subjects generated more saccades of < or = 50.1 ms to upright than to inverted faces. Patients' saccades of < or = 50.1 ms did not differ between orientations. Patterns of fixations and of saccades > 50.1 ms did not differ between groups. The results may indicate deficits in these patients in search strategies that underlie perception of facial gestalts.

Adult↗
PubMed1998

Both nicotine and mecamylamine block dizocilpine-induced explosive jumping behavior in mice: psychiatric implications.

Dizocilpine (MK-801) administration to an outbred strain of NIH Swiss mice elicits discrete episodes of explosive jumping behavior designated as "popping." This behavior may serve as a useful preclinical paradigm for the screening of potentially novel antipsychotic medications. Both nicotine and mecamylamine, a nicotinic antagonist, dose-dependently blocked dizocilpine-induced popping. The data suggest that nicotine may be of therapeutic benefit in the treatment of schizophrenia and that some of its effects may be mediated by non-nicotinic receptors.

Animals↗
PubMed1998

Visual scanning of faces correlates with schizophrenia symptomatology.

1. The purpose of this study was to examine whether quantitative measures of visual scanning of faces correlated with the severity of symptoms in patients with schizophrenia. 2. Preattentive visual fixations (fixations less than or equal to 50.1 ms in duration) were measured while 16 subjects with chronic schizophrenia and 38 comparison subjects scanned slides of human faces. 3. A significant inverse correlation was found between the number of preattentive fixations exhibited during 10 seconds of facial scanning and total Brief Psychiatric Rating Scale (BPRS) scores. 4. This study suggests that measures that probe preattentive processing during scanning of faces could represent a novel paradigm for studying the symptoms of schizophrenia.

Adult↗
PubMed1997

The antiseizure efficacies of MK-801, phencyclidine, ketamine, and memantine are altered selectively by stress.

Adaptive changes in the NMDA receptor complex occur in response to exposure to stress. We have previously shown that the ability of MK-801, an uncompetitive NMDA receptor antagonist, to antagonize electrically precipitated tonic hind-limb extension is reduced 24 h after mice are forced to swim for up to 10 min in cold water. The stress-induced reduction of the antiseizure efficacy of MK-801 stimulated the proposal that mice exposed to swim stress may serve as "an intact animal model" of altered or diminished NMDA-mediated neural transmission. In the current investigation, the dose-dependent abilities for the antagonism of electrically precipitated seizures in mice were determined for MK-801, phencyclidine, ketamine, and memantine. Interestingly, a single session of cold water swim stress reduced the antiseizure efficacies of MK-801 and memantine without affecting phencyclidine and ketamine when tested 24 h later. The data do not suggest that stress results in a simple reduction in the number of activated or open channels, but rather alters their size or charge characteristics.

Animals↗
PubMed1997

Pupillary changes associated with the development of stimulant-induced mania: a case report.

A 30-year-old cocaine-dependent man who was a subject in a study evaluating the anticraving efficacy of the stimulant medication diethylpropion (DEP) became manic during his second week on the study drug. Pupillometric changes while on DEP, especially changes in the total power of pupillary oscillation, were dramatically different than those observed in the eight other study subjects who did not become manic. The large changes in total power of pupillary oscillation occurred a few days before the patient became fully manic. Such medication-associated changes in the total power of pupillary oscillation might be of utility in identifying persons at risk for manic-like adverse effects during the medical use of psychomotor stimulants or sympathomimetic agents.

Adult↗
PubMed1997

Methylene blue adjuvant therapy of schizophrenia.

There is growing interest in the role of the nitric oxide (NO) pathway in idiopathic psychotic disorders such as schizophrenia. In this preliminary study, we examined the therapeutic efficacy of methylene blue (MB), a "downstream" inhibitor of one of NO's actions, administered orally as an adjuvant to conventional neuroleptic medications. Specifically, MB blocks NO's activation of soluble guanylyl cyclase. MB has previously been reported to have therapeutic effects in the treatment of psychosis and mania. Preclinical data also suggest that MB might possess antipsychotic potential. Participants in the current study were eight patients with schizophrenia who had incomplete responses to conventional antipsychotics (as evidenced by a Brief Psychiatric Rating Scale [BPRS] total score of 35 or more). These patients completed a 4-week open-label study with a 1 week "off", 2 week "on", and one final week "off" design. Measures of treatment efficacy were the BPRS, Schedule for the Assessment of Negative Symptoms, and Clinical Global Improvement Scale administered weekly. Final scores for each outcome measure item were based on the consensus of at least two trained raters present during each rating interview. A statistically significant, albeit modest, decrease in the severity of psychopathology was observed while the subjects were taking MB, and psychopathology significantly worsened when MB was discontinued. The results suggest a need for further study with MB or perhaps other NO-dependent guanylyl cyclase-inhibiting medications.

Adult↗
PubMed1997

Effects of nifedipine, a calcium channel antagonist, on cognitive function in schizophrenic patients with tardive dyskinesia.

We examined whether nifedipine, a calcium channel antagonist, added to a stable regimen of neuroleptic medication would affect cognition in patients with chronic schizophrenia or schizoaffective disorder who had tardive dyskinesia. Fifteen patients with tardive dyskinesia were treated with nifedipine (60 mg daily) or matching placebo for 4 weeks and then were crossed over from nifedipine to placebo or from placebo to nifedipine for another 4 weeks. At the end of each 4-week phase of the study, the patients performed a rotary pursuit test of procedural learning and a dementia scale assessing general cognitive abilities. Nifedipine improved performance in the rotary pursuit test and conceptual abilities in the dementia scale compared with placebo, but only for patients who first were exposed to the tests during the placebo condition. These results provide preliminary evidence that calcium channel antagonists might enhance learning and memory in schizophrenic patients with tardive dyskinesia.

Aged↗
PubMed1997

Behavioral approaches to the functional assessment of NMDA-mediated neural transmission in intact mice.

Altered neurotransmission mediated by L-glutamate at the level of the N-methyl-D-aspartic acid (NMDA) receptor complex has been implicated in the pathophysiologic mechanisms of several major neuropsychiatric disorders. Moreover, strategies for the pharmacologic manipulation of NMDA-mediated neural transmission have been discussed for the treatment of disorders as diverse as schizophrenia, seizures, stroke, and traumatic brain injury, MK-801, an uncompetitive allosteric antagonist of the NMDA receptor complex, was shown to antagonize electrically precipitated seizures in a dose-dependent manner and elicit popping behavior in mice. Changes in the ability of MK-801 to antagonize electrically precipitated seizures or elicit popping behavior caused by stress or pharmacologic manipulations may reflect alterations in the populations of NMDA-associated channels responsible for these behavioral actions (e.g., the number of them in the open configuration or their size, shape, and charge characteristics). We used these paradigms to study the pharmacologic actions of an allosteric glycinergic intervention (i.e., milacemide), inhibitors of the "nitric oxide cascade" (i.e., 7-nitroindazole and methylene blue), and conventional (i.e., haloperidol) and atypical (i.e., clozapine) antipsychotic medications on NMDA-mediated neurotransmission in the intact mouse. Also, marked differences in the ability of MK-801 to elicit popping behavior in inbred mouse strains suggest that they differ in their populations of NMDA receptor complexes responsible for mediating this behavior. This latter observation could lend itself to the identification of specific genetic loci contributing to this behavior. In view of the ability of phencyclidine (PCP) to precipitate a schizophreniform psychosis and the action it shares with MK-801 on NMDA-mediated neurotransmission, the characterization of these genetic loci in mice may inform the search for human loci responsible for the susceptibility to "PCP-psychosis" and schizophrenia.

Animals↗
PubMed1997

Frontal cortical atrophy and negative symptoms in patients with chronic alcohol dependence.

It has been suggested that frontal lobe pathology is associated with negative symptoms in patients with chronic alcoholism. In his exploratory study, the authors examined 19 chronic alcoholic inpatients on an alcohol treatment unit and found a significant relationship between severity of frontal atrophy (as measured by CT) and negative symptoms (as measured by the Scale for the Assessment of Negative Symptoms).

Adolescent↗
PubMed1996

Impaired motor skill learning in schizophrenia: implications for corticostriatal dysfunction.

We assessed skill learning in young and older schizophrenic patients using the rotary pursuit task. Schizophrenic patients displayed impaired learning on this task compared with normal control subjects, but older patients were not more impaired than young ones. The patients' rotary pursuit learning was not correlated to the severity of abnormal movements or to their treatment with medication, but it was associated to conceptual abilities assessed on the Dementia Rating Scale (Mattis 1988). An impairment in acquiring motor procedures in this task might reflect neuropsychological deficits associated with corticostriatal pathology.

Adult↗
PubMed1996

7-Nitroindazole and methylene blue, inhibitors of neuronal nitric oxide synthase and NO-stimulated guanylate cyclase, block MK-801-elicited behaviors in mice.

We examined the abilities of 7-nitroindazole and methylene blue, inhibitors of the neuronal isoform of nitric oxide synthase (NOS) and nitric oxide-stimulated guanylate cyclase activity respectively, to attenuate explosive episodic jumping behavior(s) ("popping") elicited by MK-801 in mice. MK-801, like phencyclidine (PCP), is a high-affinity, noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. We have postulated that MK-801-elicited popping behavior in mice represents an animal model of schizophrenia, because popping behavior is markedly inhibited/antagonized by both typical and atypical antipsychotic drugs. In the present study, popping behavior induced by MK-801 was measured using an automated detection system that quantifies vertical displacements on the testing platform. 7-Nitroindazole (100 mg/kg) and methylene blue (32 and 100 mg/kg) significantly reduced the number and force of MK-801-elicited popping behavior. Mouse rotorod performance did not differ between animals receiving 7-nitroindazole, methylene blue, or their respective vehicles, suggesting that attenuation of MK-801-elicited popping behavior was not due to either sedation or ataxia caused by 7-nitroindazole or methylene blue. Our findings suggest that nitric oxide may, in part, mediate behaviors induced by NMDA receptor antagonists, like MK-801, and that inhibitors of NOS may have antipsychotic actions.

Animals↗
PubMed1996

The competitive NMDA antagonist CPP blocks MK-801-elicited popping behavior in mice.

In the current investigation, the ability of CPP (3-(2-carboxypiperazine-4-yl) propyl-1-phosphate) to elicit mouse popping behavior in a manner similar to that of MK-801 was studied. Unlike MK-801, CPP (3.2-32 mg/kg) did not elicit any popping. The data show that a reduction in NMDA-mediated neural transmission alone is not sufficient to elicit popping behavior in mice. Moreover, pretreatment of mice with CPP attenuated MK-801's ability to elicit popping. These results suggest that popping requires the channel to be in the "active", or open, configuration and that it depends on MK-801's access and binding to its unique site in the hydrophobic channel domain.

Animals↗
PubMed1996

Evaluation of in vivo interactions in mice between flurazepam and two neuroactive steroids.

The development of neuroactive steroids as anticonvulsant medications may be useful both as a primary treatment and as an adjuvant to other anticonvulsants. They may be limited, however, by sedative and ataxic side effects. In the current study, 3 alpha-hydroxy-5 beta-pregnan-20-one and alfaxalone, two prototypic neuroactive steroids, were shown to potentiate the ability of flurazepam to antagonize electrically precipitated tonic hindlimb extension in mice at doses that by themselves had little antiseizure efficacy. While alfaxalone alone lacked motor incoordinating effects at a dose (18.0 mg/kg) that potentiated the antiseizure efficacy of flurazepam, the same dose of 3 alpha-hydroxy-5 beta-pregnan-20-one possessed both the ability to potentiate flurazepam's anticonvulsant effect and disrupt mouse rotorod performance. The data suggest that allosteric interactions that have been described in vitro between neuroactive steroids and other modulators of the GABAA receptor complex may have relevance for the intact animal. Finally, the data also suggest that neuroactive steroids could be developed as short-lived adjuvant antiseizure medications in certain critical situations (e.g., medication-refractory status epilepticus). However, the motor incoordinating effects resulting from the combination of neuroactive steroids and flurazepam suggest that their usefulness as adjuvant medications in the chronic therapy of seizure disorders may be limited.

Animals↗
PubMed1996

Lack of neurotoxic effect of diethylpropion in crack-cocaine abusers.

Dopamine agonists have been used with some success in treating cocaine addiction. However, both cocaine and psychostimulants have been reported to produce neurotoxic effects. We evaluated the effect of the stimulant diethylpropion on cognitive performance in a double-blind, placebo-controlled trial. Forty-six abstinent crack-cocaine users received either placebo, 25-mg, 50-mg, or 75-mg doses of diethylpropion. Patients were tested at baseline and again after 9-14 days of medication. There were no differences between placebo and medication groups on any test, indicating that, within the time frame studied, diethylpropion does not produce neurotoxic effects that can be detected with standardized neuropsychological tests.

Adult↗
PubMed1996

Smooth pursuit eye movements in the evaluation of famotidine adjunctive therapy of schizophrenia: a preliminary report.

Smooth pursuit eye movements (SPEM) are often abnormal in schizophrenic patients and have been proposed as a trait marker of the disorder. We explored the use of SPEM as an outcome measure in an open-label clinical trial of famotidine, an H-2 antagonist, in patients with schizophrenia; famotidine has been proposed as an adjunctive medication, particularly for negative symptoms. Prior studies using SPEM as an outcome measure have not found a significant effect with "typical" neuroleptic medication, and one study found greater SPEM dysfunction with clozapine treatment. In this study, 19 schizophrenic subjects were stabilized for at least 1 week on conventional neuroleptic medications and then administered oral famotidine, 100 mg daily, for an additional 3 weeks. SPEM and clinical measures were assessed. Whereas Brief Psychiatric Rating Scale (BPRS) and Schedule for Assessment of Negative Symptoms (SANS) scores decreased significantly with famotidine administration, there was no significant change in SPEM performance over the course of the study. Two subjects (11%) doubled their signal/noise ratio and maintained this increase after famotidine discontinuation, whereas three subjects (17%) approximately halved this ratio and returned to baseline after famotidine discontinuation. SPEM changes were not found to correlate significantly with changes in BPRS or SANS scores. These findings suggest that SPEM dysfunction reflects a "trait" rather than clinical "state" in schizophrenia, and changes in SPEM performance might not be expected always to parallel changes in clinical ratings.

Antipsychotic Agents↗
PubMed1996

An open-label study of the therapeutic efficacy of high-dose famotidine adjuvant pharmacotherapy in schizophrenia: preliminary evidence for treatment efficacy.

Histaminergic projections innervate brain areas implicated in the pathophysiology of schizophrenia. In a previous open-label study, there was the suggestion that famotidine, and H2 histamine-receptor antagonist, possessed adjuvant therapeutic properties when added to the stable neuroleptic medications regimens of 10 treatment-refractory patients. In that study, the maximal dosage of famotidine was limited to 40 mg/day, the recommended maximal dosage for the treatment of peptic ulcer disease. In this study, we examined 18 patients fulfilling DSM-III-R criteria for schizophrenia and schizoaffective disorder who had famotidine (100 mg/day) added to their stable neuroleptic medication regimen. Patients were rated on baseline, weekly thereafter, and 1 week after famotidine discontinuation, by using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Assessment of Negative Symptoms (SANS), and the Clinical Global Impression (CGI). On all of these outcome measures, statistically significant improvements suggestive of a beneficial adjunctive effect of famotidine were found. Famotidine (100 mg/day) was well tolerated by the study subjects. There was a wide range of famotidine blood levels achieved at the end of 3 weeks of famotidine adjunctive treatment, but these blood levels did not correlate with BPRS or SANS score changes. However, the patients with the greatest improvement in BPRS scores (and without concomitant deterioration in SAND scores) had some of the higher famotidine levels found in the study. Double-blind studies further assessing the potential adjunctive benefit of famotidine in the treatment of schizophrenia are indicated.

Adult↗