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Biomedical subjects

N Dafny

Publications and source records attributed to N Dafny.

At least 127 records · Page 7Linked to original sources

Does naloxone have functional significant activity on medial thalamic neurons? Microiontophoretical study.

Local administration (microiontophoretically) of naloxone was tested in 57 parafascicularis thalamic (PF) neurons of morphine-naive and morphine-dependent rats. In morphine-naive rats microiontophoretic applications of naloxone induced changes in 52% of the PF neurons. Reduction in neuronal activity was observed in the majority of them; this reduction phenomena exhibited dose response characteristics, i.e., each incremental naloxone dose caused further decrease of the neuronal discharges. In morphine-dependent animals, 64% of the PF neurons were affected. The changes seen after naloxone were mainly increases of electrical discharges (i.e. the opposite effects obtained in morphine-naive animals).

Animals↗

Dose effects of morphine on the spontaneous unit activity recorded from the thalamus, hypothalamus, septum, hippocampus, reticular formation, central gray, and caudate nucleus.

Spontaneous activity was recorded from 652 units in 8 subcortical structures of unanesthetized rats. Recordings were obtained in central gray, mesencephalic reticular formation, parafasciculus thalami, caudate nucleus, anterior and ventromedial hypothalamus, lateral septum, and dorsal hippocampus. Eighty recordings were obtained from untreated animals and 80 from saline-injected controls, none of which showed any significant changes of unit activity during the 4- 5-hr observation period. The effect of morphine, given in 5 incremental doses from 0.5 to 30.0 mg/kg ip, was followed in 492 units. Morphine enhanced or depressed spontaneous discharge rates, or caused biphasic effects, ie enhancement alternating with depression and vice versa. Naloxone induced increase in firing after either effect of morphine, or reduced spontaneous activity after morphine-induced increases. However, when morphine reduced neuronal discharges, naloxone never caused further depression. In 86 units, morphine at any dosage failed to alter neuronal activity, but in 54 of these units naloxone nevertheless induced alterations in firing rates. The pattern of responses to morphine differed between all 8 brain regions examined and was characteristic for each individual structure. This is the first systematic study describing the dose-response characteristics of morphine in 8 brain sites recorded simultaneously. Furthermore, it utilized freely behaving animals without the interference of anesthetics, which are themselves known to interact with opiates. The variety of response patterns seen supports the neuropharmacological evidence for multiple opiate receptors or multiple sites of opiate action.

Animals↗

Differential effects of interferon on ventromedial hypothalamus and dorsal hippocampus.

Three incremental doses of recombinant alpha-interferon (IF) were applied iontophoretically to hippocampal and hypothalamic cells. IF produced a dose-dependent long-lasting excitation in hippocampal neurons, whereas, in the hypothalamus alpha-IF elicited biphasic responses. The highest IF currents induced changes in the amplitude of the action potentials on both structures. Our observations suggest that IF could have a selective effect on the specific areas studied.

Animals↗

Single-cell and multiunit activity in freely moving rats after corticosterone administration.

With the purpose of correlating possible electrophysiologic changes in the brain with the negative feedback effect of glucocorticoids on neuroendocrine functions, the effects of corticosterone on multiunit (MUA) and single-cell activity in freely moving rats were studied in the hypothalamus, amygdala, and midbrain reticular formation. The hormone changed the MUA in all regions studied causing mainly an increase in the rate of firing. In the hypothalamus there was a predominance in overall inhibition, when the sensory responsiveness to acoustic stimulation was compared before and after corticosterone administration. No such effect was observed in the amygdala and midbrain reticular formation. The hormonally induced changes in MUA in the hypothalamus were confirmed by analysis of single-cell activity in the freely moving rats which showed also changes in the pattern of firing, as demonstrated by autocorrelations. These findings in the hypothalamus are significant and may represent the electrophysiologic correlates of changes in corticotrophin releasing factor in this region.

Amygdala↗

Interferon modifies morphine withdrawal phenomena in rodents.

Interferon injection in morphine dependent rats prior to naloxone treatment eliminates 7 behavioral sings of the abstinence (withdrawal) phenomenon. When a single injection of interferon was given prior to chronic morphine treatment it reduces opiate addiction liability.

Animals↗

Alteration of morphine withdrawal to naloxone by interferon.

The opiate abstinence syndrome represents a fundamental feature of the addictive process. The present study demonstrated that: 1) recombinant leukocyte A Interferon (alpha-IFN) injection prior to chronic morphine treatment reduces addiction liability; and 2) alpha-IFN and not human gamma-IFN injection to morphine dependent rats significantly modifies the naloxone-induced abstinence syndrome in a characteristic dose response manner. Two hypotheses concerning IFN's action were discussed.

Animals↗

Dorsal raphe stimulation reduces responses of parafascicular neurons to noxious stimulation.

Spontaneous activity, responses to noxious stimulation and response to electrical stimulation of the dorsal raphe were recorded extracellularly from single units in the parafascicularis (PF) nucleus in the rat. Three types of spontaneous activity were found: 'slow' firing units (1-10 spikes/sec), 'bursting' units (bursts of 2-5 spikes/10-20 msec, bursts repeat every 1-2 sec), and 'fast' firing units (15-40 spikes/sec). Noxious stimulation increased the firing rate of 63% of the slow cells and 87% of the bursting cells, while the fast firing units did not respond. Dorsal raphe (DR) stimulation decreased the firing rates of both the slow and bursting PF cells only. The degree of suppression of PF units was directly related to the frequency and intensity of the DR stimulation. When the noxious stimulus was combined with DR stimulation, DR stimulation inhibited the increase in firing rate caused by the noxious stimulus. The firing rate during combined DR stimulation and noxious stimulation averaged 51% of that during the noxious stimulation alone. In several units, DR stimulation had no effect on spontaneous activity when applied alone but did decrease the effects of noxious stimulation when applied simultaneously. The results indicate that in addition to other possible mechanisms, the DR may affect responses to noxious stimuli via an ascending modulation pathway to the parafascicularis nucleus in the thalamus.

Animals↗

Various inputs modify caudate neuronal activity.

This study investigates the input of substantia nigra (SN), dorsal raphe (DR), and medial lemniscus (ML) on caudate nucleus (CN) neurons as well as a non-specific-polysynaptic input (acoustic AC). Ninety-one units demonstrating spontaneous activity were recorded extracellularly using anesthetized rats. SN, DR, ML, and AC stimulation altered the spontaneous discharges in 79%, 90%, 86%, and 85% of the CN neurons, respectively. Only ML stimulation elicited patterns of time-locked responses in 16% of the CN units. The CN neurons showed high convergence to the four types of stimulation. Based on these results, interconnections and interrelations between SN, DR, ML, and the CN are suggested.

Animals↗

Microiontophoretically applied THIP effects upon nociceptive responses of neurons in medial thalamus.

Sprague-Dawley rats anesthetized with urethane were used to study the single cell responses of medial thalamic neurons following noxious input and their interactions with gamma-aminobutyric acid (GABA) agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and morphine sulfate applied microintophoretically . The majority of the medial thalamic neurons responded to noxious stimulation by an increase in their firing rate. Local application of both THIP and morphine attenuated the spontaneous and the noxious evoked responses of these neurons. The possibility of a role for GABA in mediating nonopiate pain suppression is discussed.

Animals↗

Electrophysiological evidence of concurrent dorsal raphe input to caudate, septum, habenula, thalamus hippocampus, cerebellum and olfactory bulb.

Field potentials evoked by electrical stimulation of the dorsal raphe nucleus (DR) were recorded in eight forebrain structures in the rat. The areas were chosen chiefly for their anatomical connections to the DR and included the olfactory bulb (OB), caudate nucleus (CN), lateral septum (Spt), lateral habenula (Hb), parafascicularis (PF), ventral thalamus (VT), hippocampus-CA1 (Hipp), and cerebellum (CB). DR stimulation evoked an initial biphasic positive-negative wave form at similar latencies in each of the eight structures. A later positive-negative-positive wave was evoked in only six structures: CN, Spt, Hb, PF, VT, and Hipp. The amplitudes and latencies of the peaks of the later wave forms varied among structures. A depth profile recording procedure created by moving the DR stimulating electrode showed that the responses in the remote structures occurred only when the stimulating electrode was located in the DR. Bursting the DR at 20 Hz for 5-20 min caused a decrease in all components of the response. The evoked potential amplitude returned to baseline levels 5-30 min after cessation of stimulation. The results indicates that the dorsal raphe has a concurrent input to many areas of the brain receiving 5HT afferents and that DR stimulation can modulate the neuronal activity in these regions.

Animals↗

Interferon modifies EEG and EEG-like activity recorded from sensory, motor, and limbic system structures in freely behaving rats.

The finding of major interest in the present experiment is that interferon injection in normal animals modifies the EEG and EEG-like activity in all the structures examined independently (unsynchronized in time). The initial effects were observed in the hypothalamus followed by limbic, somatosensory, and motor structures, respectively. The effects observed were mainly increases in the amplitude of the dominant frequency and irregular spiking. The irregular change in the amplitude remained during the six hours of the recording sessions. Complete recovery was observed twenty-four hours after drug injection.

Albumins↗

Novel effects of interferon on the brain: microiontophoretic application and single cell recording in the rat.

Interferon (IF), one of the most controversial drugs in cancer therapy, induces a variety of CNS side effects. Therefore, IF was tested on single neuronal activity and compared with other drugs. Recombinant leukocyte A IF, morphine sulfate and L-glutamate were applied microiontophoretically to 18 cortical and 29 thalamic neurons. The majority of the cortical cells were excitated by IF while most of the thalamic cells did not respond to IF; however, morphine and glutamate elicited on these neurons the expected effects. IF produced a long-lasting increase in firing discharges and exhibited dose-response characteristics.

Action Potentials↗

Response characteristics of thalamic neurons to microiontophoretically applied morphine.

The extracellular unit activity of parafasciculus thalamic neurons was studied before and after incremental microiontophoretic applications of morphine and naloxone. The parafasciculus neurons could be divided into three groups according to their initial spontaneous discharges. Only two groups responded to morphine as a function of dose and, within these groups, there were 12 different patterns. These findings suggest that the parafasciculus neurons responded in a heterogenous manner to morphine and they also provide physiological support for the biochemical evidence indicating the existence of multiple opiate receptors.

Animals↗