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Biomedical subjects

R Freedman

Publications and source records attributed to R Freedman.

At least 217 records · Page 12Linked to original sources
PubMed1982

Clonidine treatment of schizophrenia. Double-blind comparison to placebo and neuroleptic drugs.

Antipsychotic effects of clonidine were evaluated in one schizoaffective and seven schizophrenic patients, using a double-blind, cross-over design to compare placebo, clonidine, and standard neuroleptic drugs. Mean improvement on clonidine and neuroleptics was equal, and improvement scores on the two treatments were closely correlated for individual patients. Clonidine was selected because it blocks noradrenergic but not dopaminergic neurotransmission. Patients were selected because of co-existing psychosis and tardive dyskinesia, a movement disorder thought to be caused by the antidopaminergic properties of the neuroleptics. For all patients, dyskinesia improved when neuroleptics were discontinued during clonidine and placebo periods of the study. The data provide preliminary evidence that clonidine may be an effective alternative to neuroleptics, particularly for patients for whom the dopaminergic blocking action of the neuroleptics is undesirable. The study also prompts re-evaluation of theories of a unique role for dopamine in schizophrenia.

Adolescent↗
PubMed1982

Differential ethanol sensitivity of intraocular cerebellar grafts in long-sleep and short-sleep mice.

The relative importance of extrinsic and intrinsic factors for the differential sensitivity of Purkinje neurons in long-sleep (LS) and short-sleep (SS) lines of mice was investigated using cerebellar grafts to the anterior chamber of the eye. Cerebellar anlagen from fetal LS and SS donors survive and mature in oculo when grafted within and across lines. Mature cerebellar transplants from all four groups contained Purkinje cells that show sustained spontaneous discharge; excitation and inhibition are readily evoked by electrical stimulation of the surface of the graft. Superfusion of ethanol into the anterior chamber depresses Purkinje cell discharge, but neurons from LS donors are approximately 1 order of magnitude more sensitive than SS neurons; this differential sensitivity is unaltered by the host recipient line used. These data strongly suggest that the differential sensitivity of Purkinje cells to ethanol in the LS and SS mouse lines is an intrinsic property of the cerebellum.

Action Potentials↗
PubMed1982

Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia.

The action of CNS inhibitory neuronal mechanisms was tested in acutely psychotic unmedicated schizophrenic patients and in normal controls. An early positive component of the auditory average evoked response recorded at the vertex 50 msec after a click stimulus was studied. Stimuli were delivered at 10-sec intervals to establish a base-line response. Inhibitory mechanisms were then tested using a conditioning-testing paradigm by assessing the change in response to a second stimulus following the first at either 0.5, 1.0, or 2.0-sec intervals. At the 0.5-sec interval, normal controls had over a 90% mean decrement in response, whereas schizophrenics showed less than a 15% mean decrement. At 2-sec intervals, responses from normals were still 30 to 50% diminished, but those from schizophrenics showed an increased response to the stimulus compared to base line. The data suggest that normally present inhibitory mechanisms are markedly reduced in schizophrenics. Failure of these inhibitory mechanisms may be responsible for the defects in sensory gating which are thought to be an important part of the pathophysiology of schizophrenia.

Acoustic Stimulation↗
PubMed1981

Electrophysiologic interactions of antipsychotic drugs with central noradrenergic pathways.

The pathway from the nucleus coeruleus to Purkinje neurons in rat cerebellar cortex was used to analyze effects of antipsychotic neuroleptic drugs on a central noradrenergic pathway. Fluphenazine and haloperidol produced a dose-dependent increase in Purkinje neuron spontaneous discharge. This effect was not seen in animals in which the noradrenergic input had been removed by the neurotoxin 6-hydroxydopamine. In contrast, the effects of neuroleptics were still present in animals which had received neonatal X-ray irradiation, which destroys intrinsic inhibitory and excitatory pathways in cerebellar cortex. Chlorpromazine produced the same increase in discharge rate, but was significantly less potent. alpha-Flupenthixol was equipotent with fluphenazine, but beta-flupenthixol, a behaviorally inactive stereoisomer, was without effect. The dose-response curves showed potencies similar to those in several animal behavioral paradigms. In addition, the rank order of potency was identical to that in clinical tests of antipsychotic activity. Three-week chronic administration of fluphenazine resulted in complete blockage of noradrenergic activity, with no further increase in Purkinje neurons spontaneous discharge rate by additional doses of drug. Thus, tolerance does not develop to the noradrenergic blocking effect of the neuroleptic. Taken together, this evidence suggests that antipsychotic neuroleptic drugs block noradrenergic neurotransmission in the CNS.

Animals↗
PubMed1981

Differential electrophysiological and behavioral responses to optically active derivatives of phencyclidine.

Dextro- and levorotatory isomers of 1-(1-phenylcyclohexyl)-3-methylpiperidine (PCMP) were synthesized. Both isomers inhibited spontaneous cerebellar Purkinje neuron firing when applied locally by pressure ejection. This effect was dose-dependent, with the (+)-isomer about 5--7 times more potent than the (-)-isomer. Both isomers also depressed rotarod performance in mice. Again, the (+)-isomer was about 5 times more potent than the (-)-isomer. Both rotarod performance and Purkinje cells discharge were depressed maximally 10--15 min after i.p. injection of drug. Our results suggest a correlation between behavioral performance and central neuron electrophysiological activity and suggest that the central actions of PCP or its derivatives are probably mediated at one locus, by a stereospecific mechanism.

Animals↗
PubMed1981

Ethanol-induced depressions in cerebellar and hippocampal neurons of mice selectively bred for differences in ethanol sensitivity: an electrophysiological study.

The recently discovered profound differential sensitivity of cerebellar Purkinje (P) cells in long-sleep (LS) verus short-sleep (SS) mice to the depressant effects of locally applied ethanol was extended in this study. First, the sensitivity of Purkinje neurons from HS mice (an outbred stock of mice from which the LS and SS lines were derived), was found to be almost exactly intermediate between the values for the long-sleep and short-sleep animals. Second, no differential sensitivity in long-sleep versus short-sleep hippocampal pyramidal neurons was observed. This was true using both spontaneous and evoked activity. Third, no differential sensitivity of P cells was seen in long- versus short-sleep mice with local application of halothane. Taken together with previous reports, these data strongly suggest that whatever genetically determined central nervous alterations result in the differential soporific effects of ethanol in the two (LS and SS) mouse lines, such alterations are brain region- and depressant drug-specific rather than generalized.

Action Potentials↗
PubMed1981

Changes in noradrenergic neurotransmission in rat cerebellum during aging.

This study compared the electrophysiological effects of locally applied cyclic adenosine-mono-phosphate (N6cAMP) between Purkinje neurons from young (4-month) and old rats (15-months and older). Purkinje neurons from young rats were significantly more sensitive to locally applied norepinephrine and N6cAMP than neurons from old rats. GABA sensitivity between the two groups was unaltered. Our results suggest that the locus of the adrenergic subsensitivity observed in older animals may reside to a large extent at or beyond the level of cAMP generation.

Aging↗
PubMed1981

New selective agent for isolation of Pseudomonas aeruginosa.

Results of minimal inhibitory concentration tests with a diversity of bacterial strains showed that 9-chloro-9-(4-diethylaminophenyl)-10-phenylacridan (C-390) inhibited the growth of all microorganisms tested (other than Pseudomonas aeruginosa) at 25 microgram/ml or less, whereas MICs obtained for P. aeruginosa ranged from to to greater than 100 microgram/ml. Therefore, C-390 was evaluated as a potential selective agent for P. aeruginosa in pseudomonas agar F. Recovery tests were conducted on this medium with 53 strains o P. aeruginosa, and the results were compared to those obtained in similar tests on commercially available selective media, i.e., pseudomonas isolation agar and Pseudosel agar. The results of these comparisons indicated that pseudomonas agar F with C-390 was significantly less inhibitory than Pseudosel agar and pseudomonas isolation agar and more selective than pseudomonas isolation agar. The incorporation of C-390 in pseudomonas agar F also provided a medium that was both selective and differential. Preliminary evidence also suggested that C-390 may be added to other basal media with comparable results.

Acridines↗
PubMed1980

Age-related electrophysiological changes in rat cerebellum.

The spontaneous discharge of cerebellar Purkinje neurons was studied in 3-, 12-, 15-, and 20-month-old rats. Fluphenazine and haloperidol administered intraperitoneally produced a dose-dependent increase in the spontaneous discharge in 3-month-old animals, but were ineffective in 12-, 15- and 20-month-old rats. Intraperitoneal administration of amphetamine resulted in a dose-dependent decrease in spontaneous Purkinje neuron discharge in 3-month-old rats without affecting neurons from the older animals. Discrution of norepinephrine afferents by 6-OHDA or reserpine increased spontaneous discharge rate in 3-month-old animals. This treatment did not affect Purkinje neurons in 12-, 15- and 20-month-old rats. Local application of drug with the same multibarreled electrode revealed that neurons from older rats were significantly less sensitive to inhibition by norepinephrine than were Purkinje neurons from 3-month-old animals. Similar application of GABA did not reveal a differential sensitivity. For locus coeruleus activation to produce 50% inhibition in Purkinje neuron discharge, significantly higher stimulation currents were required in 15-month-old rats than in 3-month-old animals. Our results suggest a decreased postsynaptic sensitivity to norepinephrine in 12-, 15- and 20-month-old rats as compared to 3-month-old animals.

Aging↗