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Biomedical subjects

R B Rosse

Publications and source records attributed to R B Rosse.

At least 37 records · Page 2Linked to original sources
PubMed1996

D-cycloserine adjuvant therapy to molindone in the treatment of schizophrenia.

This preliminary investigation examined the therapeutic efficacy of two doses of oral D-cycloserine (5 and 15 mg p.o. b.i.d.) administered as an adjuvant to molindone (150 mg p.o. q.d.) in the treatment of schizophrenia. D-Cycloserine is an agonist at the N-methyl-D-aspartate (NMDA) subclass of glutamate receptor complex. An NMDA agonist intervention was studied because of the schizophreniform psychosis precipitated by phencyclidine (PCP), which is a noncompetitive antagonist at the NMDA glutamate receptor. The PCP model of schizophrenia is regarded as the most comprehensive pharmacological model of this disorder. In this preliminary, placebo-controlled, double-blind, parallel-group study, the measures of treatment efficacy were the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms, and Clinical Global Impression Scale. The final scores for each item of the outcome measures employed were based on the consensus of at least two trained raters who were present during each rating interview. In the 13 subjects evaluated, although the D-cycloserine was well tolerated, neither dose seemed to possess adjuvant therapeutic efficacy. However, since another recent report of nine patients with schizophrenia treated for 2 weeks with a slightly higher dose of D-cycloserine (50 mg/day) described significant clinical and neuropsychological improvement, further study of the adjuvant potential of slightly higher doses of D-cycloserine seems warranted. Additionally, there might be a therapeutic window for D-cycloserine dosing, as daily doses of 250 mg have been associated with symptom worsening.

Administration, Oral↗
PubMed1996

A measure of pupillary oscillation as a marker of cocaine-induced paranoia.

Cocaine-induced paranoia (CIP) remains an important drug-induced model of idiopathic paranoia for which no psychophysiologic marker has yet emerged. Measures of pupillary oscillation were able to significantly distinguish a group of abstinent crack cocaine abusers endorsing past CIP (n = 32) from another group of crack addicts who denied past CIP (n = 29).

Adult↗
PubMed1995

Interference with nitric oxide production and action potentiates the antiseizure efficacy of flurazepam.

The effect of inhibiting "downstream" consequences of NMDA receptor stimulation with 7-nitroindazole, an inhibitor of the neuronal form of nitric oxide synthase (NOS), and methylene blue, an inhibitor of the nitric oxide (NO)-sensitive soluble guanylyl cyclase, on electrically precipitated tonic hindlimb extension in mice was studied. Moreover, the abilities of these compounds to potentiate the antiseizure efficacy of flurazepam were also examined. When administered alone, 7-nitroindazole (10.0-100 mg/kg) and methylene blue (1.0-100 mg/kg) did not share the ability of MK-801 (0.1 to 1.0 mg/kg) to antagonize electrically precipitated tonic hindlimb extension. However, doses of MK-801 (0.18 mg/kg), 7-nitroindazole (100 mg/kg), and methylene blue (10.0 and 100 mg/kg) that were devoid of apparent antiseizure efficacy by themselves potentiated the ability of flurazepam to antagonize electrically precipitated seizures. NMDA receptor antagonists cause neuronal toxicity, interfere with acquisition of spatial memory and induction of long-term potentiation in the hippocampal CA1 region, and precipitate psychoses in susceptible individuals. Thus, the development of both open-channel blockers of the NMDA receptor complex that can be administered in lower doses, and inhibitors of the "downstream" consequences of NMDA receptor-gated transient elevations of intraneuronal calcium ions as potential adjunctive antiseizure medications should be considered. Moreover, administration of these compounds with benzodiazepines may attenuate some of the neurotoxicity that may result from NMDA receptor antagonism.

Analgesics↗
PubMed1995

Diethylpropion pharmacotherapeutic adjuvant therapy for inpatient treatment of cocaine dependence: a test of the cocaine-agonist hypothesis.

Fifty cocaine-dependent patients completed a 2-week double-blind, double-dummy, parallel-group comparison of four dosage levels of diethylpropion and placebo. This clinical trial was designed to evaluate both diethylpropion's ability to attenuate cocaine cue-induced craving and its potential for development as a medication with cocaine-agonist properties. The results indicated that diethylpropion was not superior to placebo and confirmed earlier reports that craving for cocaine diminishes over the course of an inpatient hospitalization. Moreover, the results showed that the cocaine cue-induced craving paradigm employed is effective in stimulating craving for cocaine. Medications that are effective in attenuating this type of "conditioned" craving may have relevance to the breaking of the cycle of relapse and long-term treatment of cocaine dependence. Diethylpropion may not be an appropriate candidate for future medication development because of its lack of obvious therapeutic efficacy and the emergence of a significant number of side effects. However, a cocaine-agonist medication strategy may be appropriate for a subgroup of cocaine-dependent patients with coexisting attention deficit-hyperactivity disorder.

Adult↗
PubMed1995

Famotidine adjunctive pharmacotherapy of schizophrenia: a case report.

Recent reports suggest some utility for famotidine, a histamine type 2 (H2) antagonist, in the treatment of schizophrenia. The current report describes a treatment-resistant patient with chronic undifferentiated schizophrenia whose most dramatic symptomatic improvements were temporarily related to the open-label addition of famotidine (40-100 mg/day) to conventional neuroleptic treatment (molindone 150-200 mg/day) over the course of approximately 10 months. During one 2-week interval, his symptoms were controlled with famotidine (40 mg/day) alone. The case suggests that some adjuvant efficacy exists for famotidine in at least some patients with schizophrenia. Placebo-controlled trials are needed to more fully evaluate the utility of famotidine in the treatment of schizophrenia.

Famotidine↗
PubMed1995

Computerized measurement of MK-801-elicited popping and hyperactivity in mice.

MK-801, a high-affinity phencyclidine (PCP) analogue, is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptor that elicits hyperactivity, stereotypic behaviors, and "popping," an explosive episodic jumping behavior, in mice. The schizophreniform psychosis precipitated by PCP in humans has stimulated interest in studying MK-801-elicited mouse behaviors for their potential development as animal models of idiopathic psychosis. We describe a computerized method for measuring popping and hyperactivity elicited by MK-801 in mice, based on vertical displacements of a platform. This computerized procedure allows for the automatic measurement of discrete "pops" per individual episode of popping behavior, the force of each one of the explosive jumps, and the duration of discrete episodes of popping; these latter measures could not be easily ascertained by visual inspection alone. Moreover, the computerized measurements facilitate quantitative evaluation of the effects of pharmacological manipulations on MK-801-elicited popping. For example, the antipsychotic haloperidol was shown to reduce significantly both MK-801-induced popping and hyperactivity. Ideally, MK-801-elicited mouse popping and hyperactivity will serve as a useful preclinical screening paradigm for potential antipsychotic medications. Additionally, it is hoped that the use of this automated system will contribute to a greater understanding of the mechanisms of MK-801-induced popping and hyperactivity.

Analysis of Variance↗
PubMed1995

Anxiety and pupil reactivity in cocaine dependent subjects endorsing cocaine-induced paranoia: preliminary report.

There has been the clinical impression that people with higher levels of anxiety and central arousal are more prone to develop cocaine-induced paranoia (CIP), but this notion has not been formally studied. In the current study, we examined the differences between 28 CIP-endorsing and 16 CIP-denying chronic cocaine users in their levels of state and trait anxiety as measured by the Spielberger State-Tait Anxiety Inventory. We also studied levels of central arousal and reactivity using pupil size measures both during exposure to neutral, abstract, non-drug cues, and after exposure to a cocaine cue. Levels of trait (but not state) anxiety were significantly higher in the CIP group than in the non-CIP group. Moreover, while there were no significant pupil size differences or changes between the two groups while viewing neutral, abstract video images, the CIP group had significantly greater pupillary dilation in response to a video image of crack cocaine than did the non-CIP group. These significant differences remained even after covarying for anxiety scores. The study findings seem relevant to studies of autonomic reactivity in response to drug cues in cocaine-dependent patients; such studies might remain attentive to potential cue reactivity differences between patients endorsing and those denying CIP. Finally, this is the first study showing higher trait anxiety in patients with CIP.

Adult↗
PubMed1995

The nitric oxide pathway: potential implications for treatment of neuropsychiatric disorders.

The freely diffusible gaseous compound nitric oxide (NO) has recently been discovered to be an important cellular messenger in many organ systems throughout the body. The importance of NO as an intermediary in cell communication in the brain is highlighted by the fact that the excitatory amino acid glutamate, the most abundant central neurotransmitter, is an initiator of the reaction that forms NO. In this article, background information about the discovery of NO, its biochemistry, and a brief summary of some of its peripheral and central actions are given to provide a complete picture of this remarkable novel second messenger. We also discuss how an improved understanding of NO pathway may lead to the identification of novel medications for the treatment of a number of neuropsychiatric conditions, including memory deficits, pain, drug addiction, seizures, bipolar disorder, psychosis, eating disorders, and the treatment of the sequelae of various brain injuries.

Animals↗
PubMed1994

Saccadic distractibility in cocaine dependent patients: a preliminary laboratory exploration of the cocaine-OCD hypothesis.

Epidemiologic Cachment Area Survey (ECAS) results suggest that cocaine abusing patients are at increased risk for the later development of Obsessive Compulsive Disorder (OCD), and a need for attention in laboratory and clinical research to the 'cocaine-OCD hypothesis' has been described. Analysis of the ECAS data, however, could not rule out the possibility of a 'distinctive OCD-like syndrome' related to cocaine use. Such an OCD-like syndrome in cocaine dependent individuals has been recently described, where some cocaine dependent patients compulsively forage for cocaine, especially after a cocaine binge. To further explore a possible relationship between cocaine dependence and OCD, the performance on an antisaccade task of 32 cocaine dependent individuals was compared to a group of 15 individuals without neuropsychiatric or substance abusing histories. OCD patients have been described as having a greater frequency of reflexive glances (i.e., increased saccadic distractibility) during the antisaccade task than normals. No statistically significant differences in antisaccade performance were observed between the cocaine dependent patients and a normal comparison group. However, when the cocaine using group was divided into those endorsing and those not endorsing significant cocaine-induced compulsive foraging, statistically significant differences emerged. Cocaine-induced compulsive foragers had the poorest antisaccade performance. While the small sample sizes and the lack of an OCD control group limit the conclusions that can be drawn from the present study, the results seem to suggest that a cocaine-OCD link might be particularly relevant for those cocaine addicts endorsing compulsive foraging.

Adult↗
PubMed1994

L-tyrosine pharmacotherapy of schizophrenia: preliminary data.

The utility of L-tyrosine (10 g/day in four divided doses) as an adjuvant to molindone (150 mg/day) in the treatment of schizophrenia was investigated using a placebo-controlled, double-blind crossover design (3 weeks on L-tyrosine, 3 weeks on placebo). The objective of this inpatient study was to increase dopaminergic neural transmission along mesocortical projections in patients by increasing the precursor availability of L-tyrosine for dopamine biosynthesis. Theoretically, this approach might lessen both negative and positive symptoms of schizophrenia and improve frontal lobe-mediated neuropsychological performance. There was no evidence of statistically significant improvement conferred by L-tyrosine as measured by weekly Brief Psychiatric Rating Scale (BPRS), Schedule for the Assessment of Negative Symptoms (SANS), or Clinical Global Impressions (CGI) scales. The 12-h trough plasma level of L-tyrosine was significantly higher in all patients during the L-tyrosine phase of the study (t = -3.9, df = 20, p = 0.0009). At the end of each 3-week study period, no significant differences could be found in Wisconsin Card Sorting Test (WCST) or memory test performance. Smooth-pursuit eye movement (SPEM) performance had significantly more saccadic intrusions during the L-tyrosine supplementation phase compared to the placebo period. This increase in saccades during SPEM suggests that the tyrosine supplementation might have had some central effect.

Adult↗
PubMed1994

Environmental stress-induced functional modification of the central benzodiazepine binding site.

The central benzodiazepine binding site mediates the therapeutically relevant pharmacologic actions of benzodiazepine agonists, including reducing anxiety, sedation, muscle relaxation, and antagonism of seizure production. Benzodiazepines potentiate the ability of gamma-aminobutyric acid (GABA) to promote membrane chloride ion conductance by binding reversibly to a distinct site on the GABAA receptor complex. Although the role of this central benzodiazepine binding site in mediating the pharmacologic actions of benzodiazepine agonists has been shown conclusively, its participation in an animal's response to stress is less certain. Data are reviewed consistent with an environmental stress-induced modification of the structure and function of the central benzodiazepine binding site. Modifications show brain anatomic regional selectivity. The mechanisms of these modifications include rapid enzyme-mediated phosphorylations of the GABAA receptor complex and the selective transcription of individual polypeptide subunits. The potential relevance of the data on environmental stress-induced functional modifications of the central benzodiazepine binding site to the development of newer medications and improved understanding of the pathophysiology of stress-related neuropsychiatric disorders is discussed.

Animals↗
PubMed1994

Nimodipine pharmacotherapeutic adjuvant therapy for inpatient treatment of cocaine dependence.

Recent preclinical studies suggest utility for voltage-sensitive calcium channel blockers (VSCCBs) in the treatment of cocaine addiction. The following double-blind placebo-controlled study examined the role of the VSCCB nimodipine in attenuating cocaine craving in 66 recently abstinent cocaine-dependent patients on an inpatient substance abuse treatment unit utilizing an intensive 12-step milieu-oriented psychosocial therapy. While the medication was well tolerated, the dose of nimodipine used in this study (90 mg q.d.) was not superior to placebo in reducing background or cue-induced cocaine craving over the 3 weeks of the study. There was the suggestion that nimodipine might attenuate the severity of some cocaine-induced brain deficits, as detected by evaluation of smooth pursuit eye movement function. A rationale for evaluating higher doses of nimodipine for the treatment of cocaine addiction is presented. As nimodipine might have anticraving and mood-stabilizing properties and cardio- and neuroprotective properties in the face of cocaine intoxication and might possibly even reverse some cocaine-induced brain deficits, further investigation of the role of nimodipine (and other VSCCBs) in cocaine addiction appears an attractive avenue of future medication development.

Calcium Channel Blockers↗
PubMed1994

Phenomenologic comparison of the idiopathic psychosis of schizophrenia and drug-induced cocaine and phencyclidine psychoses: a retrospective study.

Both stimulant-induced and phencyclidine (PCP)-induced psychoses have been proposed as models of the idiopathic psychosis of schizopherenia. In this two-part study, the phenomenology of the psychosis associated with a period of cocaine intoxication was evaluated retrospectively in 34 male crack cocaine-dependent patients without concomitant psychiatric disorder and then was compared with the psychosis of 16 actively psychotic schizophrenic men (without a history of drug or alcohol abuse in the past year). Certain First Rank Schneiderian Symptoms (FRSS) were more commonly observed in the schizophrenic patients (e.g., thought broadcasting, thought withdrawal) than in the cocaine addicts. In the second part of this study, we retrospectively examined the cocaine and PCP experiences of an additional 22 cocaine addicts who had a past history of separate periods of cocaine and PCP use. Overall, the frequency of FRSS recalled during periods of cocaine and PCP intoxication was similar. However, the psychosis related to cocaine intoxication was more associated with an intense suspiciousness and paranoia related to a fear of being discovered or harmed while using cocaine. PCP-induced psychosis was less associated with suspiciousness and more associated with delusions of physical power, altered sensations, and unusual experiences [e.g., out of body experiences, experiencing religious figures or events directly (e.g., being with Noah at the time of the Arc)]. As elements of both cocaine and PCP psychosis can be found in schizophrenia, a model integrating the mechanisms of several psychotogenic drugs may be more informative. Such an integrative model might better capture the heterogeneity of psychotic symptoms that can be seen in schizophrenia. Furthermore, different pharmacologic interventions (e.g., "anti-stimulant" versus "anti-PCP") might address different aspects of the positive symptom picture in schizophrenia.

Adult↗
PubMed1994

The relationship between cocaine-induced paranoia and compulsive foraging: a preliminary report.

Two prominent behavioral syndromes associated with chronic cocaine use that have been described in the literature are cocaine-induced paranoia (CIP) and cocaine-induced compulsive foraging (CICF) for cocaine. To help to clarify the relationship between the two cocaine-induced syndromes, the concordance and sequence of onset of the two cocaine-induced behaviors over the course of the patients' lifetime use of cocaine and during the course of a binge was examined in 62 crack cocaine-dependent men. Thirty-four (54.8%) reported experiencing both CIP and CICF. In 18 (29%) of the patients, only one of these cocaine-induced behavioral syndromes was reported. Ten (16.1%) of the subjects reported neither CIP nor CICF. Patterns of cocaine or other substance use and degrees of tolerance to cocaine were not significantly different between the groups endorsing different patterns of cocaine-induced behaviors. CIP typically preceded the onset of CICF both over the course of the patients' lifetime use of cocaine and over the course of a binge. The study results suggest varying thresholds for the expression of these behaviors in chronic cocaine-abusing individuals.

Adult↗
PubMed1994

Gaze discrimination in patients with schizophrenia: preliminary report.

The authors administered a gaze discrimination task to 24 patients with chronic schizophrenia and 25 subjects with no psychiatric history. Each subject was shown slides and asked, "Is the person in the slide looking directly at you?" Patients with schizophrenia were more likely than comparison subjects to perceive the person in the slide as looking at them when the person was looking away. Because there is evidence that gaze discrimination performance involves the superior temporal sulcus region of the brain and this region has been implicated in theories about the pathogenesis of schizophrenia, further study of the gaze discrimination task seems indicated.

Adult↗
PubMed1993

Transient compulsive foraging behavior associated with crack cocaine use.

Compulsive foraging behavior associated with use of crack cocaine involves compulsively searching the environment for possibly misplaced pieces of crack. Of 41 crack cocaine addicts evaluated, 33 (80.5%) reported at least some compulsive foraging associated with use of crack; 21 (51.2%) reported such behavior as always associated with crack use. The mean length of time spent in compulsive foraging was 90 minutes. Cocaine-induced foraging may represent a drug-induced model of a type of compulsive behavior.

Adult↗