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Biomedical subjects

R Freedman

Publications and source records attributed to R Freedman.

At least 199 records · Page 11Linked to original sources
PubMed1984

Differential effects of phencyclidine upon hippocampal complex-spike and theta neurons.

The effects of local application of phencyclidine (PCP) upon hippocampal CA1 neurons were investigated in urethane-anesthetized rats. Hippocampal neurons were classified on the basis of extracellularly recorded action potential duration as either complex-spike or theta cells prior to PCP administration. PCP depressed spontaneous firing of 46 of 48 complex-spike cells, but excited 12 of 13 theta neurons. This result demonstrates that hippocampal complex-spike and theta neurons may be differentiated of theta neurons were greatly attenuated or absent in rats pretreated with DSP4, a neurotoxin which selectively destroys noradrenergic pathways. This latter finding lends additional support to the hypothesis that the effects of locally applied PCP are mediated via noradrenergic mechanisms.

Animals↗
PubMed1984

Effects of the selective noradrenergic neurotoxin DSP4 on cerebellar Purkinje neuron electrophysiology.

The effect of the adrenergic neurotoxin DSP4 on cerebellar electrophysiology was studied in the rat. DSP4, administered parenterally, depleted cerebellar norepinephrine by 76%. The depressant response of cerebellar Purkinje neurons to phencyclidine, a drug which acts on adrenergic presynaptic terminals to release NE, was markedly reduced after DSP4 pretreatment. In contrast with 6OHDA, which increased firing rates of the Purkinje cells, DSP4 did not change the rate or pattern of Purkinje cell discharge. Taken together these results suggest that DSP4 may be a valuable tool for studying central adrenergic pathways, but that this drug has properties which differ from 6OHDA.

Amines↗
PubMed1984

Deficits in sensory gating in schizophrenic patients and their relatives. Evidence obtained with auditory evoked responses.

A deficit in inhibitory gating of auditory evoked responses was examined in 15 schizophrenic patients, their first-degree relatives, and normal subjects, using a conditioning-testing paradigm with the P50 wave of the auditory evoked response. This paradigm demonstrates inhibition by presenting paired stimuli to the subject; the P50 wave evoked by the second stimulus is reduced because of inhibitory mechanisms activated during the response to the first stimulus. In normal subjects, the mean amplitude of the second P50 response was reduced to less than 20%. In the schizophrenics, the mean amplitude of the second response was more than 85% of the first, a result that replicates our previous finding of a deficit in inhibition in schizophrenia. Approximately half the first-degree relatives, generally including at least one parent, had a similar deficit. Presence of this deficit in the parents was associated with a family history of schizophrenia. Family members with this deficit also had significantly higher scores on several scales of the Minnesota Multiphasic Personality Inventory than did family members without the deficit. Despite the deficit in inhibition, other characteristics of the P50 wave were normal in the relatives, in contrast to unmedicated schizophrenics, who showed additional abnormalities in wave latency and amplitude.

Acoustic Stimulation↗
PubMed1984

Interminable treatment in patients who appear healthy.

Treatment interminability among nonpsychotic psychiatric patients is a subject not well understood. Those who treat such patients are often nagged by a feeling that they are somehow failing, especially if the patient has a history of personal achievement. The authors describe three such patients and propose that they exemplify a type of pseudomaturation. common features in the accounts of their childhood suggest a failure in the separation-individuation phase of development. The authors theorize that this failure first contributed to the development of psychiatric symptoms during adulthood and then to interminability in treatment.

Adult↗
PubMed1984

Further reflections on changes in fertility expectations and preferences.

In this paper we have shown that the statements made in our original paper and disputed by Sloane and Lee are not ". . . . .at least partially in error." Concerning the first two areas of disagreement, Sloane and Lee's analysis did not address the conclusions that we reached and, therefore, could not refute them. In the first instance the observations of Sloane and Lee are useful in understanding how one of the effects we observed occurred, but in the second area the usefulness of their analysis is not at all clear. The third area of disagreement resulted because Sloane and Lee paid insufficient attention to the observed sample relationships and used a statistical test that is inefficient for the type of data used. Of course, our disagreement is not with log-linear methodology, but with its inappropriate application and interpretation by Sloane and Lee. In two instances they used results from the log-linear procedures to address issues that could not be addressed by those particular results, and in another instance they used a log-linear test of statistical significance when a more efficient alternative provides a different picture. The problems associated with the Sloane and Lee analysis illustrate the importance of precise specification of the substantive issues being investigated and the careful interpretation of the substantive implications of the original data and statistical results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Presynaptic dopaminergic activity of phencyclidine in rat caudate.

This study tested the hypothesis that phencyclidine (PCP) is an indirect dopamine (DA) agonist in the caudate nucleus. Single caudate neurons in rats anesthetized with urethane were recorded extracellularly with multibarrel micropipettes. Effects of drug solutions, applied by pressure microejection, were measured as changes in spontaneous and evoked neuronal activity. Caudate neurons were classified according to their latency-to-discharge in response to supramaximal cortical stimulation. PCP inhibited the spontaneous activity of 92% of neurons with latencies less than 13 msec, while DA inhibited 87%. Both drugs inhibited evoked activity significantly less than spontaneous activity (P less than .01). Neurons with latencies greater than 13 msec were excited by DA significantly more often (45%) than by PCP (13%; P less than .05). Receptor stereospecificity is suggested by the finding that the (+)-isomer of the 3-methyl piperidine derivative of PCP was significantly more potent than the (-)-isomer for inhibition of spontaneous activity. Mg++, which blocks presynaptic release of neurotransmitter, significantly antagonized inhibitory effects of PCP on spontaneous activity, which suggests a presynaptic effect of PCP. DA, which acts postsynaptically, was much less affected by Mg++. The potency of PCP was significantly less in rats treated with reserpine or 6-hydroxydopamine than in control rats, suggesting the endogenous DA is required for the action of PCP. Fluphenazine and (+)-butaclamol, potent DA-receptor antagonists, blocked the effect of PCP, but (-)-butaclamol did not. These results support the hypothesis that PCP facilitates release and/or inhibits reuptake of DA in nerve terminals and thereby acts as an indirect DA agonist in the caudate. However, there may be a subpopulation of caudate neurons in which PCP acts by a nondopaminergic mechanism.

Animals↗
PubMed1983

Effects of dopamine on spontaneous and evoked activity of caudate neurons.

This study examined the effects of dopamine (DA), pressure ejected from multi-barrelled micropipettes, on the spontaneous and evoked activity of caudate neurons, recorded extracellularly in rats anesthetized with urethane. Neurons were categorized according to their discharge latencies in response to supramaximal cortical stimulation: neurons which fired with latencies less than 13 msec were classified "short-latency-discharge neurons", while neurons with latencies greater than or equal to 13 msec were classified "long-latency-discharge neurons". This procedure also allowed the detection of neurons with low levels of spontaneous activity. The predominant effect of DA on both neuronal types was inhibition of spontaneous activity. However, DA exerted a modulatory effect in that spontaneous activity was inhibited at "doses" which did not affect activity evoked by cortical stimulation. Although DA-induced excitation was infrequent, it was significantly more prevalent among long-latency neurons than among short-latency-discharge neurons. Long-latency-discharge neurons were also significantly more spontaneously active than were short-latency neurons. In rats depleted of endogenous DA by treatment with reserpine, caudate neurons had significantly increased rates of spontaneous and evoked activity, shorter duration of stimulus-evoked inhibition, and longer latency for evoked discharges than in control rats. These results suggest that DA exerts modulatory effects on caudate neuronal activity. Furthermore, these results suggest that short- and long-latency-discharge neuronal groups may consist of pharmacologically, as well as physiologically, distinct neuronal types.

Action Potentials↗
PubMed1983

Plasma homovanillic acid and tardive dyskinesia during neuroleptic maintenance and withdrawal.

Plasma levels of homovanillic acid (HVA), a dopamine metabolite, were examined in 19 psychiatric inpatients during maintenance treatment on neuroleptic medications. A significant positive correlation was found between the level of HVA and the severity of tardive dyskinesia (TD) in these patients. Seven patients had their medication discontinued for 12 days. In spite of a fall in neuroleptic levels to negligible values, plasma HVA levels remained essentially stable while scores on the Abnormal Involuntary Movement Scale (AIMS) fell only slightly. The data support the hypothesis that some forms of TD may involve a persistent increase in presynaptic dopaminergic activity.

Adult↗
PubMed1983

Altered mood and norepinephrine metabolism following withdrawal from alcohol.

Affective symptoms were evaluated in chronic alcoholics during a 2-week period following detoxification from alcohol. Increased ratings were apparent both on the Manic State Rating Scale (MSRS) and on the Ma Scale of the Minnesota Multiphasic Personality Inventory (MMPI) in a subgroup of these patients. Primary symptoms included grandiosity, irritability, and mildly increased psychomotor activity. Alcoholics who had been detoxified for several months or hospitalized medical patients did not show similar symptoms. Measurements of urinary 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), a metabolite of norepinephrine which has been associated with manic-depressive illness, also showed increased excretion in a subpopulation of recently detoxified patients. The coexistence of depressed mood in these patients may have led to symptoms of hypomania being previously overlooked, although signs of depression are common in mania itself.

Alcoholism↗
PubMed1983

Partial resolution of tardive dyskinesia with treatment of co-existing thyrotoxicosis.

Neuroleptic-induced tardive dyskinesia improved after treatment of thyrotoxicosis. Neuroleptic blood levels indicated that the improvement was not caused by masking of the symptoms by rising drug levels. Dopamine metabolite measurements suggested that the thyrotoxicosis caused an increase in the sensitivity of caudate neurons to dopamine, rather than a change in release of dopamine.

Dopamine↗
PubMed1983

Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: comparison of medicated and drug-free patients.

Central nervous system inhibitory neuronal mechanisms were assessed in clinically stable chronic schizophrenic patients treated with neuroleptic drugs to provide data for comparison with those obtained previously from acutely psychotic, unmedicated patients. An early positive component of the auditory average evoked response recorded at the vertex 50 msec after a click stimulus (P50) was studied. After stimuli were delivered at 10-sec intervals to establish a baseline response, inhibitory mechanisms were assessed in a conditioning-testing paradigm, by measuring 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 an 80% mean decrement in response, whereas schizophrenics showed a mean decrement of less than 10% but there was no significant difference in suppression between medicated and unmedicated patients. However, the amplitude of P50, which was smaller in unmedicated schizophrenics than in normal subjects, was significantly increased in the medicated patients. The data suggest that inhibitory mechanisms which are dysfunctional in acutely psychotic.

Acoustic Stimulation↗
PubMed1983

Neurophysiological studies of sensory gating in mania: comparison with schizophrenia.

The action of central nervous system mechanisms involved in sensory gating was assessed in acutely psychotic manic patients. 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. Sensory gating mechanisms were then tested using a conditioning-testing paradigm to assess the change in response to a second stimulus following the first at either 0.5-, 1.0- or 2.0-sec intervals. A similar paradigm had been used previously to assess deficits in this function in acute and chronic schizophrenics. We found a deficit in sensory gating in acutely manic patients. similar to that found in schizophrenics, although the variability in response was more marked in the manic patients. We followed these patients during their treatment on lithium carbonate and found a return of these neuronal functions towards normal values which corresponded to their clinical improvement. A series of stable euthymic bipolar patients were found to have responses indistinguishable from normal controls. The data suggest that deficits in neuronal gating functions, similar to those found in schizophrenia, can be seen during acute mania but these deficits return to normal as the acute psychosis abates.

Adolescent↗
PubMed1982

Persistent effects of amphetamine on cerebellar Purkinje neurons following chronic administration.

The spontaneous discharge of cerebellar Purkinje neurons was studied in rats after withdrawal from chronic treatment with amphetamine (2 mg/kg per day x 21 days). Discharge rates in withdrawn animals remained significantly lower than those of controls for up to 50 days. Disruption of the adrenergic input to these neurons from the locus coeruleus by treatment with propranolol, clonidine or reserpine, partially restored these discharge rates. Acute administration of amphetamine in amphetamine-withdrawn rats did not further depress Purkinje neurons discharge rate, whereas in a previous study in this lab, Purkinje neurons from naive animals were markedly slowed. Moreover, Purkinje neurons from amphetamine-withdrawn rats were also significantly less sensitive than controls to locally applied norepinephrine. These results demonstrate that chronic amphetamine can lead to very long-term changes in neuronal activity, and suggest that these changes may be mediated, in part, by the noradrenergic transmitter systems.

Action Potentials↗
PubMed1982

Interactions of a neuroleptic drug (fluphenazine) with catecholamines in hippocampus.

The interactions of fluphenazine with the electrophysiological responses to catecholamines were studied in the rat hippocampus and parietal cortex. In the in vitro hippocampal slice, changes in synaptically evoked responses induced by norepinephrine, isoproterenol and dopamine were not altered by superfusion of fluphenazine. Both alpha- and beta- components of adrenergic responses were unaffected by neuroleptic administration in this preparation. Similarly, alterations in the spontaneous firing of single hippocampal pyramidal neurons in situ to adrenergic agonists or dopamine were not affected by local fluphenazine and administration using pressure ejection through multibarreled micropipettes. In contrast, norepinephrine- or isoproterenol-induced inhibitions of parietal cortical neurons in situ were potently antagonized by fluphenazine. A similar interaction was observed from a hippocampal basket neuron. It is concluded that while fluphenazine can antagonize well-defined noradrenergic effects in some brain regions (e. g., cerebellum, cortex), this property is not generalized to all brain regions receiving noradrenergic input.

Animals↗
PubMed1982

Interactions between phencyclidine and cholinergic excitation of hippocampal pyramidal neurons.

The interaction between phencyclidine and acetylcholine-evoked responses of hippocampal pyramidal neurons was investigated in normal and catecholamine-depleted rats. Phencyclidine antagonized the acetylcholine-induced excitations in both preparations. However, in the majority of cases, this effect was observed only at doses of phencyclidine which also manifested nonspecific membrane stabilization. In contrast, phencyclidine-induced decreases in firing rate, which have been shown to be mediated by catecholamines, occurred at doses of phencyclidine which do not cause local anesthesia. Taken together, these data suggest that the catecholaminergically-mediated effects of phencyclidine may be more important in the hippocampus.

Acetylcholine↗