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Biomedical subjects

R Freedman

Publications and source records attributed to R Freedman.

At least 235 records · Page 13Linked to original sources
PubMed1980

Conditions for adrenergic hyperinnervation in hippocampus: I. Histochemical evidence from intraocular double grafts.

The developing hippocampal anlage of rats was homologously grafted to the anterior chamber of the eye of adult recipients. After intraocular maturation of the hippocampal graft and removal of the sympathetic innervation of the eye by ipsilateral superior cervical ganglionectomy, four types of monoamine neurons were transplanted to the eye chamber: Peripheral sympathetic neurons, central adrenergic neurons of locus coeruleus, central dopaminergic neurons of substantia nigra, and central 5-hydroxytryptamine neurons of the lower raphe nuclei. All four classes of monoamine neurons were able to reinnervate the hippocampal graft, but the fiber ingrowth differed markedly. Although peripheral sympathetic neurons produced a pattern of adrenergic innervation in the hippocampal graft which resembled innervation of the hippocampus by the locus coeruleus in the brain, locus coeruleus neurons themselves produced an extremely dense plexus of fibers within the graft. This hyperinnervation remained intact for up to 9 months, the longest period of time studied. The locus coeruleus graft itself received fibers from the hippocampus graft, as demonstrated by the retrograde transport of horseradish peroxidase. We conclude that the hippocampal graft exerts a much stronger growth stimulation on the locus coeruleus neurons than on the peripheral sympathetic neurons. The difference between innervation patterns suggest that both presynaptic and postsynaptic influences determine fiber ingrowth in the central nervous system.

Adrenergic Fibers↗
PubMed1980

Conditions for adrenergic hyperinnervation in hippocampus: II. Electrophysiological evidence from intraocular double grafts.

Following sequential intraocular transplantations of areas containing NE cell bodies (locus coeruleus or superior cervical ganglion) and of NE fiber target areas (hippocampus), both pieces mature in a manner analogous to that observed for individual transplants. NE-containing nerve fibers, derived from either LC or SCG transplants, can be seen to invade the hippocampal formation. When LC is used, the invading fibers markedly hyperinnervate the hippocampus while SCG-derived fiber densities approximate those seen with innervation from the adrenergic ground plexus of the iris. Electrophysiological recordings from neurons in the LC reveal an atropine-sensitive excitatory response to illumination, suggesting innervation of the LC by cholinergic nerve fibers from the iris. This is supported by the fact that dense cholinesterase-positive staining can be found in the LC piece. Application of an epileptogenic agent, such as penicillin, results in a marked excitation of neurons in the LC without inducing epileptiform activity in the hippocampus. In contrast, single hippocampal grafts seize readily after penicillin. Local application of the inhibitory agent GABA into the LC allows penicillin-induced epileptiform activity to generate in the hippocampus, suggesting that functional inhibitory innervation develops between NE fibers derived from LC and pyramidal neurons in the hippocampus. Supporting this, subsequent excitation of LC neurons by iontophoresis of glutamate terminates the hippocampal seizure. Prior administration of reserpine (2.5 mg/kg) disrupts the inhibitory influence of LC innervation on the hippocampal EEG following penicillin. After reserpine, the hippocampal portions of double grafts behave like single hippocampal transplants. It is concluded that sequential transplantations of cell body and target regions of the CNS to the anterior chamber of the eye creates a functional, yet isolated, neuronal pathway which can be utilized to study the development of neuronal connections.

Adrenergic Fibers↗
PubMed1980

Electrophysiological actions of neurotensin in rat cerebellum.

The electrophysiological actions of neurotensin (NT) and its analog D-Arg9-NT were studied in rat cerebellar Purkinje neurons. NT applied by pressure ejection was a potent depressant of Purkinje (P) neuron firing. In contrast, iontophoretically applied NT was a weak depressant. Pressure-ejected D-Arg9-NT, which is largely inactive in peripheral systems, had little effect on P neurons. The depressant effects of pressure-ejected NT were blocked by intraperitoneally administered haloperidol, iontophoretically applied magnesium or 6-OHDA pretreatment. After such treatments, locally applied NT evoked only excitations. The results of this study suggest that NT, when applied by pressure ejection, produces two effects on the Purkinje neuron. The potent inhibitory effects of locally applied NT appear to result from release of the inhibitory transmitter, norepinephrine from locus coeruleus-derived afferents. We postulate that the excitations, which appear when postsynaptic effects of norepinephrine are antagonized or release is reduced, may be the direct result of NT action at the postsynaptic P neuron membrane.

Action Potentials↗
PubMed1980

Electrophysiological evidence for presynaptic actions of phencyclidine on noradrenergic transmission in rat cerebellum.

The actions of the psychotomimetic drug phencyclidine (PCP) were studied using Purkinje neurons in the cerebellum of urethane-anesthetized rats. PCP, applied by micropressure ejection through multibarreled micropipettes, depressed the spontaneous activity of these neurons as recorded by extracellular electrophysiological techniques. This depressant effect was blocked by neuroleptic drugs and lithium, both of which also block the depressant effects of norepinephrine, but not those of gamma-aminobutyric acid. PCP-elicited depressions could not be obtained in rats in which the cerebellar noradrenergic terminals had been lesioned selectively by pretreatment with the neurotoxin 6-hydroxydopamine. However, PCP was still an effective depressant in animals after destruction of non-noradrenergic intrinsic excitatory and inhibitory interneurons which synapse on the Purkinje cell by neonatal X-irradiation. Further treatment of the X-irradiated animal with 6-hydroxy-dopamine resulted in Purkinje neurons which were not responsive to PCP. Administration of magnesium ions, which reduces the release of neurotransmitters from afferent terminals, also blocked the depressant effects of PCP. The results of this study suggest that PCP acts in the cerebellum by a presynaptic mechanism involving the release of norepinephrine from intact, functioning noradrenergic terminals.

Animals↗
PubMed1980

Effects of acute and chronic amphetamine treatment on Purkinje neuron discharge in rat cerebellum.

The spontaneous discharge of the cerebellar Purkinje neuron in urethane-anesthetized rats is used as an indicator of central noradrenergic activity during the acute and chronic administration of d-amphetamine. Acute parenteral administration of amphetamine causes a dose-dependent slowing of the discharge. Since this effect is not seen in animals in which the catecholaminergic innervation has been selectively removed by previous treatment with 6-hydroxydopamine, it is hypothesized that the slowing is caused by the increased release and/or blocked reuptake of endogenous norepinephrine. Acute administration of amphetamine also increases the response of the Purkinje neurons to its afferent inputs: the excitatory climbing fibers and the inhibitory basket and stellate cells. These effects of amphetamine on spontaneous and evoked activity are similar to the effects of microiontophoretically applied norepinephrine. After daily treatment for 5 days with amphetamine, there is no change in the response to acutely administered amphetamine. After 21 days of treatment, discharge rates before and after acute administration are both significantly lower than in acutely treated controls. Administration of the beta adrenergic antagonist propranolol returns the discharge rate to control levels in these chronically treated animals. Chronic amphetamine treatment may thus cause an increase in response to endogenous norepinephrine, both when spontaneously released and when released after acute amphetamine administration.

Action Potentials↗
PubMed1980

Changes in fertility expectations and preferences between 1962 and 1977: their relation to final parity.

Changing fertility expectations and preferences from 1962 to 1977 are compared with final parity in a longitudinal study. Results are strongly affected by initial parity in 1962. Final parity, 27 percent below expectations for those initially childless, illustrates the effect for couples free to change expectations downward of declining fertility preferences. Changes in expectations early in marriage had a significant long-term effect on final parity, as did early differences between wife's expectations and husband's preferences. unplanned births increased final parity significantly. Religion, education, and income had no systematic relation to the discrepancy between initial expectations and final parity.

Family Characteristics↗
PubMed1979

Seizures and related epileptiform activity in hippocampus transplanted to the anterior chamber of the eye: modulation by cholinergic and adrenergic input.

Transplants of rat hippocampus into the anterior chamber of the eye of a host animal were used to assess the effects of cholinergic and adrenergic neuronal inputs on the generation and duration of seizure activity. Cholinomimetics initiated both seizures and hypersynchronous neuronal activity in the transplants. Cyclic guanosine monophosphate (GMP) derivatives and isobutyl methylxanthine elicited similar changes. Reflex activation of the cholinergic parasympathetic input to the iris and transplant by illumination of the ipsilateral retina also induced seizures or increased the rate of penicillin-induced interictal spike discharge. Application of beta-adrenergic agonists inhibited interictal spikes and paroxysmal depolarizing shifts induced by penicillin. Fluorescence histochemical studies showed that host sympathetic adrenergic fibers derived from the ground plexus of the iris invaded the transplant to form fine varicose nerve terminals. Activation of these adrenergic afferents to the transplant diminished both the amplitude and frequency of penicillin-induced epileptiform activity. Epileptiform activity in hippocampal occular transplants is strongly modulated by cholinergic and adrenergic neuronal inputs, with the former exerting a facilatory influence and the latter, an inhibitory effect.

Adrenergic Fibers↗
PubMed1979

Patients' awareness of extrapyramidal reactions to neuroleptic drugs: possible evidence for the role of catecholamines in perception.

The awareness of extrapyramidal reactions during initiation of neuroleptic treatment was studied in 14 patients. Only one patient spontaneously identified the presence of dystonia. The other 13, including 3 who had experienced extrapyramidal reactions during previous hospitalizations, did not fully identify the presence of symptoms, although several had vague discomfort. There was marked variability in acknowledgement of symptoms in response to prompting by staff members. The findings are similar to reports of agnosia for hemiparesis after parietal lobe injury and also to descriptions of agnosia in animals caused by destruction of dopaminergic neurons. Since extrapyramidal reactions represent blockade of dopaminergic neurotransmission, patients' inability to perceive the reactions may represent evidence for catecholaminergic modulation of sensory perception.

Adolescent↗
PubMed1979

Modulatory actions of norepinephrine in the central nervous system.

Early studies have shown that norepinephrine (NE) released synaptically or iontophoretically onto neurons in the central nervous system acts to depress firing by a mechanism associated with a hyperpolarization but no change or an increase in membrane resistance. This in contrast to classical transmitters, which cause hyperpolarization by a conductance increase. Recent studies designed to clarify the functional implications of these biophysical actions have revealed new phenomenons in which the major overall effect of NE on cerebellar Purkinje cells is to enhance conventional synaptic input and induce an increase in signal-to-noise ratio of evoked versus spontaneous activity. NE released iontophoretically or via stimulation of the locus coeruleus also has been found to enhance the inhibitory effects of gamma-aminobutyric acid, an endogenous cerebellar transmitter. The effects appear even at low doses of NE having no direct depressant action on spontaneous activity. Specificity tests have shown no enhancement of glycine-induced inhibition by NE and an inability of dopamine to mimic NE. The hypothesis is presented that a significant action of NE in the central nervous system is to induce a bias that alters postsynaptic responsiveness to conventional transmitter systems, which themselves may be more directly concerned with detailed information transfer.

Animals↗
PubMed1979

Do intentions predict fertility? The experience in Taiwan, 1967-74.

Are responses to survey questions about desire for additional children useful in predicting future fertility? Data from Taiwan covering the years 1967--74, a period of rapid fertility decline and increasing contraceptive practice, indicate that reproductive intentions and contraceptive use were very good predictors of subsequent fertility. Whether more children were wanted was itself the most important determinant of contraceptive use. Aggregate consistency between attitudes and behavior was higher than found in US surveys during the same period. Similar studies are needed to determine whether statements of intentions have predictive value in other settings as well.

Adolescent↗
PubMed1979

Some roots of preference: roles, activities and familial values.

This paper examines some of the connecting links between modernization in a developing society, particularly urbanization and increased education for women, and preferences for number of children. Using 1973 Taiwan data, preferences for smaller families are found to be consistently related to modern attitudes and behavior in the three domains examined: intrafamilial husband-wife role relationships, extrafamilial activities of the wife, and familial and religious values relating the family to the larger institutional setting. Modernization of these attitudes, behaviors, and values has an impact on reproductive goals independent of their association with structural variables. The wife's outside activities and exposure to modern influences through the mass media are especially important linkages, having a particularly strong mediating effect in the education effect on preferences. Intrafamilial relations appear to be of less importance. Modernization of familial and religious values mediates between urbanization and family size preferences. The measure of preference used is a scale value which has been found in other research to be more predictive of reproductive behavior than the conventional single-valued statement of number of children wanted. As the level of contraceptive use rises in developing societies, family size preferences increasingly become a factor in birth rates, and understanding the sources of change in these preferences takes on added importance. The policy implications of these findings are discussed.

Attitude↗
PubMed1978

Paranoid symptoms in patients on a general hospital psychiatric unit. Implications for diagnosis and treatment.

Paranoid symptoms were found in 40% of patients admitted to a university general hospital psychiatric unit during a ten-month period. Fifty-eight percent of this group had frank paranoid delusions, while the rest had ideas of reference or generalized suspiciousness. Only one half of those who had paranoid delusions had paranoid schizophrenia. A significant number had affective disorders or organic brain disorder. Ideas of reference and suspiciousness were found in many patients who were not psychotic. The therapeutic implications of these findings are reported in three patients who were inadequately treated for affective disorders because the presence of paranoid symptomatology had led to an incorrect diagnosis of schizophrenia.

Adult↗