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Biomedical subjects

N Dafny

Publications and source records attributed to N Dafny.

At least 73 records · Page 4Linked to original sources
PubMed1991

Focal dorsal raphe stimulation and pinnal electrical stimulation modulate spontaneous and noxious evoked responses in thalamic neurons.

This study investigated the nocieceptive responses of single neurons within the nucleus parafascicularis (PF) thalami of the rat following two modes of electrical stimulation known to induce analgesia. It was found that both focal electrical dorsal raphe stimulation (DRS) and bilateral pinnal (ear) electrical stimulation (PES) converge on the same PF neurons, affecting both the spontaneous discharges and the noxious evoked responses toward these neurons. The effects of different stimulus current intensity, frequency and pulse duration were also examined. It was found that for both DRS and PES at pulse frequency of 10 Hz and current amplitude of 10 microA are the optimal parameters to modulate both the spontaneous and the noxious evoked responses. These stimuli produced prolonged effects related to the duration of stimulation. The external (PES) low current stimulation which was delivered below the sensory threshold was as effective in modulating noxious responses as the invasive DRS in intact animals and in animals with bilateral dorsolateral-funiculus ablation. It was observed that dorsal lateral funiculus ablation (DLFx) did not modify the DRS and the PES effects. These observations further support the existence of an ascending pain modulation pathway.

Animals↗
PubMed1990

Trans-cranial electrical stimulation attenuates abrupt morphine withdrawal in rats assayed by remote computerized quantification of multiple motor behavior indices.

The goal of the present study was to assess the effects of trans-cranial electrical stimulation on the behavioral signs of the abrupt withdrawal syndrome of rats. However, this goal also necessitated the introduction of an experimental model measuring animal behavior for prolonged periods of time using a computerized animal activity monitoring system to quantify spontaneous motor activities associated with abstinence behavior. Comparable withdrawal severity was obtained by both the activity monitoring system and investigator observation of motor signs of abstinence behavior. Moreover, using this system we demonstrate a time-dependent effect of electrical stimulation in reducing the severity of various indices of motor hyperactivity associated with abrupt morphine withdrawal in rats.

Animals↗
PubMed1990

Microiontophoresis of cocaine, desipramine, sulpiride, methysergide, and naloxone in habenula and parafasciculus.

The effects of microiontophoretically applied cocaine, desipramine (DES), sulpiride (SUL), methysergide (METH), and naloxone (NAL) on the responses of physiologically identified single neurons in the habenula (Hab) and parafasciculus thalami nucleus (PF) were examined in rats. Three cell types were identified in both nuclei on the basis of the responses obtained following noxious stimulation that were classified as "nociceptive-on," "nociceptive-off," and "nonnociceptive" cells. Administration of cocaine generally resulted in a decrease in the firing rate of nociceptive-on and nonnociceptive neurons in both Hab and PF. In contrast, cocaine generally induced an excitation in the baseline firing of the nociceptive-off cells. Cocaine application concomitant with noxious stimulation prevented the evoked responses of the nociceptive-on and the nociceptive-off cells. DES, when applied alone, was found to induce excitation in neuronal discharge of all three cell types in both sites. Combined application of cocaine with DES resulted in no observable change in discharge frequency for the nociceptive-on and nonnociceptive cells, while inducing an additive excitatory effect on the nociceptive-off cells. SUL, in contrast, induced no observable effect on baseline firing when given alone, yet consistently antagonized cocaine-induced effects on all three cell types. Finally, METH and NAL induced no effects on baseline firing or cocaine-induced modifications in neuronal discharge frequency.

Animals↗
PubMed1990

Effects of microiontophoretic application of cocaine, alone and with receptor antagonists, upon the neurons of the medial prefrontal cortex, nucleus accumbens and caudate nucleus of rats.

The spontaneous extracellular electrical activity of 102 neurons, within the caudate nucleus (CN), medial prefrontal cortex (MPC), nucleus accumbens (NAc) and a control site, the lateral thalamic nucleus (LT), was studied. Cocaine depressed spontaneous activity in the majority of the cells studied from all regions except the lateral thalamus. Desipramine, which has been used clinically for the treatment of withdrawal of cocaine, also depressed neuronal activity in the caudate nucleus. In addition, of the three receptor antagonists tested, sulpiride, methysergide and naloxone, only the dopamine antagonist (sulpiride) affected cocaine-induced neuronal responses. This study further emphasizes the emerging importance of midbrain dopaminergic systems in the pharmacological effects of this important drug of abuse.

Animals↗
PubMed1990

Microiontophoretic application of muramyl-dipeptide upon single cortical, hippocampal and hypothalamic neurons in rats.

Muramyl-dipeptide (MDP), a metabolite of bacterial cell walls, has a variety of biological effects, including the induction of acute phase serum glycoproteins and fever, and the promotion of slow wave sleep. Muramyl-dipeptide and other products, derived from immune responses, may act directly in the CNS to recruit secondary autonomic and endocrine responses to disease. To test this hypothesis the properties of single neuron discharges, following local application (microiontophoresis) of MDP within the somatosensory cortex, the dorsal hippocampus and the medial basal hypothalamus were studied in rats. The results obtained from cortical (N = 30), hippocampal (N = 28) and hypothalamic (N = 32) neurons demonstrated a direct effect of MDP upon all three regions of the brain. In addition, MDP modified the responses of these same neurons to morphine. These results support a role of MDP in the process of neuro-immune modulation and further demonstrate an interaction between lymphoid agents and opioids in the CNS.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Muramyl-dipeptide, a macrophage-derived cytokine, alters neuronal activity in hypothalamus and hippocampus but not in the dorsal raphe/periaqueductal gray of rats.

Muramyl-dipeptide (MDP) is derived in vivo by degradation of bacteria cell walls and is the minimum fragment that stimulates the acute phase response to bacterial infection. The present study investigates whether this specific product of an immune response affects central nervous system (CNS) function. To this end, the activity of single neurons within the hypothalamus, hippocampus, and dorsal raphe/periaqueductal gray region prior to and following systemic (i.p.) injection was studied. The results obtained from a total of 120 cells demonstrate that single hypothalamic and hippocampal neurons, sites previously shown to aid in the integration of various environmental stimuli into physiologic processes, alter their neuronal activity in site-specific manners following MDP administration. The specificity of the responses included both the threshold for activation of particular sites, effects of increasing dosages upon response pattern characteristics, and time course to the changes observed. These results therefore suggest that MDPs may play a role in the neuro-immunologic regulatory pathways during the immune response to bacterial infection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

The brain and the immune system: an intact immune system is essential for the manifestation of withdrawal in opiate addicted rats.

Gamma irradiation (500 rad) is often used to suppress the immune system in mice, rats and man. Recently, it was shown that irradiation prior to chronic morphine treatment, dramatically reduces the severity of naloxone-precipitated withdrawal in morphine-dependent animals. In the present study adoptive transfer of 2-6 x 10(8) splenocytes to irradiated rats prior to chronic morphine treatment restored the severity of all withdrawal signs precipitated by naloxone. In contrast, adoptive transfer of fractionated splenocyte subpopulations only partially restored withdrawal severity; and transfer of irradiated splenocytes, red blood cells or diluted numbers of normal splenocytes did not have any observed restorative effect. These findings suggest that specific cellular activities or factors derived from lymphoid cells are required for the expression of opiate withdrawal.

Animals↗
PubMed1990

Modification of nociceptively identified neurons in thalamic parafascicularis by chemical stimulation of dorsal raphe with glutamate, morphine, serotonin and focal dorsal raphe electrical stimulation.

The properties of local application of glutamate, morphine and serotonin in the dorsal raphe (DR) area and the effects of DR electrical stimulation on the spontaneous activity and on the nociceptive responses of 135 parafascicularis (PF) neurons were studied. It was observed that local glutamate application within the DR exerts an effect upon the "nociceptive-on" PF neuronal activity similar to that induced by focal electrical stimulation of the DR in intact animals and in animals after dorsal spinal cord section. In addition, local application of morphine and serotonin in the DR area elicits different effects on the spontaneous activity versus the nociceptive responses of PF neurons. These observations suggest that opioids and serotonin at least in part participate in modulation of pathways from DR to PF. This observation is consistent with the hypothesis that the DR ascending path modulates nociceptive input to the PF (at least in part) via activations of both opioid and serotonergic receptors.

Action Potentials↗
PubMed1990

Habenular neuron responses to noxious input are modified by dorsal raphe stimulation.

Single-cell experiments were undertaken to characterize the neurons of the rat habenular complex (Hab) which respond to noxious input and the extent to which the noxious responses can be modulated by dorsal raphe stimulation. The reported observations demonstrate that habenular neurons exhibit two response patterns to noxious stimulation termed 'nociceptive-on' and 'nociceptive-off'. In addition, it was demonstrated that dorsal raphe stimulation modulates the noxious input to the 'nociceptive-on' and to the 'nociceptive-off' cells. These findings demonstrated that the habenular complex responds to noxious input and, together with other findings reporting that both direct morphine application into the Hab and electrical stimulation of the Hab produced analgesia, suggest that the habenular complex is integrated into the pain regulatory circuitry.

Animals↗
PubMed1990

Hypothalamic neuronal activity associated with onset of pseudopregnancy in the rat.

The electrical activity of several hypothalamic sites, before and following cervical stimulation, was examined in an attempt to evaluate the central nervous system processes involved in the induction of pseudopregnancy in the rat. Cervical stimulation, resulting in pseudopregnancy, induced a sequence of neuronal changes at: 3.8, 4.4, 11.6, 20.1, 30.8, 44.5, 51.2, 51.7, 62.4, 85.1 and 111.5 min after stimulation in the preoptic area, lateral hypothalamus, ventromedial hypothalamus, preoptic area, suprachiasmatic nucleus, lateral hypothalamus, preoptic area, ventromedial hypothalamus, lateral hypothalamus and anterior hypothalamus, respectively. These results suggest that the preoptic region contains both the facilitatory neuronal mechanism and also an inhibitory system. The latter could tonically inhibit the expression of the nocturnal prolactin surge. We conclude that the sequence of neuronal events observed in various hypothalamic areas is in part responsible for the process which results in pseudopregnancy.

Animals↗
PubMed1990

Restraint stress modulates sensory evoked potentials.

The present experiment investigated whether repeated exposure to an acute stressor elicits changes in sensory evoked responses recorded from awake rats. Animals were restrained for four hours per day on each of four consecutive days. Recordings were obtained on the day prior to the first restraint and following the first and fourth day of restraint. Restraint generally resulted in an increase in the amplitude of sensory evoked responses recorded from the medial basal hypothalamus (MBH), dorsal hippocampus (DH), and superior colliculus (SC) without changing any other characteristics of the recording. A persistent increase in the averaged evoked response amplitudes seen on both the first and fourth daily presentation of the stressor indicates that no significant adaptation to the stressor occurred over this time period as measured electrophysiologically.

Animals↗
PubMed1989

Trans-cranial electrical stimulation attenuates the severity of naloxone-precipitated morphine withdrawal in rats.

The expression of morphine withdrawal in rats has been demonstrated as dependent upon the integrity of specific brain regions. Focal intracranial electrical stimulation of some of these sites results in the attenuation of withdrawal severity. The present study demonstrates that electrical auricular stimulation, in a paradigm known to attenuate nociceptive responses of several brain nuclei, attenuates the severity of naloxone-precipitated morphine withdrawal in rats. This simple non-invasive treatment, based on long-standing principles of electroacupuncture, may provide a useful adjunct for therapy of the narcotic withdrawal syndrome.

Animals↗
PubMed1989

Suppression of opiate withdrawal by cyclosporin A and dietary modification.

It has been demonstrated in a murine model that a defined diet (Purina Basal Diet 5755) has immunosuppressive effects similar to cyclosporin A (CsA). It was also shown that CsA treatment in opiate dependent rats can attenuate the severity of opiate withdrawal. In this study, an opiate dependence model was established in Balb/c mice to assess the effects of the 5755 diet and CsA on morphine withdrawal - a CNS mediated phenomenon. Three groups of mice were used; a chow-fed control group (Purina 5008), a chow fed CsA treated group, and a group maintained on the 5755 diet. Morphine dependence was established by subcutaneous implantation of a 100 mg morphine base pellet under ether anesthesia. Seventy-two hours after pellet implantation, withdrawal was precipitated by a single injection of the opiate antagonist naloxone (2 mg/kg ip). Two indicators of withdrawal were assessed; jumping and diarrhea. The data demonstrated that both CsA and the 5755 diet resulted in significant attenuation of withdrawal symptoms with the 5755 diet being the most effective of the two. These findings suggest that immune modulation elicited by the 5755 diet and CsA treatment has a direct impact on the CNS opioid function.

Animals↗
PubMed1989

The immune system and opiate withdrawal.

Whole body exposure to 500 rad ionizing irradiation suppresses the immune system in rats. Moreover, when administered prior to chronic morphine treatment, irradiation exposure also dramatically reduces the severity of naloxone-precipitated withdrawal in morphine dependent animals. The reinstillment of 2-6 x 10(8) normal lymphoid immunocompetent cells to irradiated rats by adoptive transfer prior to chronic morphine treatment restores all withdrawal signs precipitated by naloxone injection. The data suggest that specific cellular activities or factors derived from lymphoid cells are required for the expression of opiate withdrawal, indicating that the immune system participates in the manifestation of opiate dependence.

Animals↗
PubMed1989

Dorsal raphe stimulation, 5-HT and morphine microiontophoresis effects on noxious and nonnoxious identified neurons in the medial thalamus of the rat.

In single cell experiments, the characterization of the responses of medial thalamic neurons to noxious and nonnoxious stimulation was made to examine the effects of two substances involved in pain, morphine and 5-HT, and the action of one pain suppressor mechanism, dorsal raphe stimulation. Single cell activity was recorded in urethane anesthetized rats. Tail pinch and tail immersion in hot water were used as nociceptive stimuli. Skin strokes, air puffs and hair brushing were used as nonnociceptive stimuli. Morphine, 5-HT microiontophoresis and dorsal raphe stimulation were performed in all the recorded units. Fifty-eight percent from 61 medial thalamic recorded units responded both to noxious and nonnoxious stimulation; whereas only 18% and 24.6% of the units responded exclusively to noxious and nonnoxious stimulation, respectively. The noxious responding units were located in the most posterior portions of the medial thalamus. Dorsal raphe stimulation and 5-HT ejection prevented the excitation elicited by noxious input. Morphine ejection prevented both the noxious and nonnoxious input in medial thalamus, in a different population as compared to dorsal raphe stimulation or 5-HT ejection. These findings support the existence of a pain ascending mechanism mediated by an opioid-serotonergic interaction in the medial thalamus of the rat.

Action Potentials↗
PubMed1989

Nociceptive responses in nucleus parafascicularis thalami are modulated by dorsal raphe stimulation and microiontophoretic application of morphine and serotonin.

Single-cell experiments were undertaken to examine the hypothesis that serotonin (5-HT) and morphine participate in ascending pain suppression phenomena. The observations demonstrate that: 1) dorsal raphe stimulation (DRS) modulates the spontaneous activity and the noxious-evoked responses of parafasciculus (PF) neurons, and the modulating effects of DRS are altered by either naloxone or methysergide; 2) morphine ejection into the PF alters the spontaneous activity and the noxious-evoked responses of PF neurons, and naloxone prevents morphine effects; and 3) serotonin ejection into the PF alters the spontaneous activity and the noxious-evoked responses of PF neurons and methysergide prevents the serotonin effects. These findings support the hypothesis that opioid and serotonin participate, at least in part, in the control of ascending pain mechanisms.

Action Potentials↗