Search PubMed⌕ Search

Biomedical subjects

N Dafny

Publications and source records attributed to N Dafny.

At least 91 records · Page 5Linked to original sources
PubMed1989

Noxious and non-noxious responses in the medial thalamus of the rat.

Single-cell experiments were undertaken to localize and characterize the medial thalamic (MT) neurons which respond to noxious and non-noxious input in the rat. The observations demonstrated that: (1) 61 and 42% of MT neurons respond to noxious (Nox) and non-noxious (NN) stimulation, respectively; (2) MT neurons exhibit 4 cell types according to their pattern of response; Type A units were excited exclusively by Nox stimulation; Type B units were excited exclusively by NN stimulation; Type C units were excited by both (Nox and NN) stimulation, and Type D units exhibited decreases in firing rate following both stimulation modalities; (3) neurons of the parafascicularis nucleus exhibit more noxious responses (Type A units) than other medial thalamic areas.

Action Potentials↗
PubMed1988

Immune response products alter CNS activity: interferon modulates central opioid functions.

The present report provides evidence to support the hypothesis that peptides released during an immune response alter CNS activity and thus may provide a means for the immune system to transmit afferent signals into the brain. Specifically, it is demonstrated that recombinant interferon-alpha (rIFN-alpha), a peptide associated with the immune response to viral infection, can alter opiate withdrawal severity in a dose-dependent manner upon direct injection into brain areas essential for this phenomenon. These results are compared and contrasted with the effect of systemically injected rIFN-alpha upon opiate withdrawal. In addition, an electrophysiological investigation into the basis of the interaction of opioids and rIFN-alpha in brain structures essential for the expression of opioid activities is also presented. Finally, the effects of rIFN-alpha upon the functions of both the CNS and other systems is discussed in terms of the effects reported for other peptides associated with immune responses.

Animals↗
PubMed1988

Neuroimmune intercommunication, central opioids, and the immune response to bacterial endotoxin.

Muramyl dipeptide is the smallest biologically active fragment of the lipopolysaccharide (LPS) moiety of gram-negative bacteria cell walls. The present report demonstrates that this product, associated with the immune response to bacterial infection, can modify CNS activity. Specifically, it is demonstrated that 6-0-stearoyl-muramyl dipeptide (MDP) can attenuate opiate withdrawal severity in a dose-dependent fashion when injected directly into areas of the brain essential for this phenomenon. In addition, MDP alters both baseline and postnarcotic electrophysiologic responses of four brain areas essential for various opioid activities. Similar findings have been reported for interferon-alpha (IFN-alpha), a peptide associated with the immune response to virus. Yet, even though MDP and IFN are shown to exert similar effects on opioid activity, there are also some very distinct differences in the actions of both of these immune response products. These observations suggest that central opioid systems may provide targets for the perception as well as the differentiation of afferent immunologic sensory input to the brain.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Dorsal raphe and external electrical stimulation modulate noxious input to single neurons in nucleus parafascicularis thalami.

Spontaneous discharges and nociceptive responses of 47 parafascicularis thalami (PF) neurons were recorded extracellularly and comparisons were made between the effects of these discharges following focal dorsal raphe stimulation (DRS) and bilateral pinnal electrical stimulation (PES). Eighty-three percent of PF neurons (N = 39) responded to noxious stimulus, about 69% of the PF responsive cells (N = 27) were excited during noxious stimuli and thus categorized as "nociceptive-on" cells. The remaining 31% (N = 12) were suppressed by the noxious stimuli, and were categorized as "nociceptive-off" cells. DRS and PES attenuated the spontaneous activity of the "nociceptive-on" neurons as well as the noxious input to these cells, while the spontaneous activity of the "nociceptive-off" cells was suppressed only following DRS and not following PES. Moreover, PES displayed disinhibiting properties, namely, it reduced the suppression effects elicited by noxious input. In conclusion, it was demonstrated that both focal DRS and noninvasive PES were effective in modulating pain input to single neurons in the PF.

Animals↗
PubMed1988

Cholecystokinin: induced suppression of feeding in fed, fasting and hypothalamic island rats.

Experiments were undertaken to examine the involvement of CCK in the regulation of feeding behavior. The results indicate that 1) intact normal animals exhibited rhythmic circadian feeding behavior, with onset of feedings starting about two hr prior to dark period and continuing until 1 to 2 hr prior to the light period; 2) food deprivation and surgical isolation of the hypothalamus after this pattern of feeding behavior, to the point that animals spend more time eating with no identifiable pattern; 3) administration of CCK to either fed, fasted or hypothalamic island animals has a profound dose related effect on suppressing feeding behavior and in modifying the eating pattern over 24 hr. A possible involvement of CCK with the opiate system in controlling feeding behavior is discussed.

Animals↗
PubMed1988

Cyclosporine affects central nervous system opioid activity via direct and indirect means.

It is demonstrated that cyclosporine (CsA), a novel fungal-derived immunosuppressive agent, attenuates naloxone-precipitated morphine withdrawal in an unusual dose-dependent manner following direct intracerebroventricular (icv) administration. However, comparison and contrast of this effect of CsA following icv versus ip administration demonstrates that although CsA does alter the severity of withdrawal by a direct effect within the CNS, the agent is most effective when given systemically. It is also demonstrated that CsA alters the electrophysiologic properties of discrete brain nuclei both when given alone and when given concomitant with morphine and naloxone.

Animals↗
PubMed1988

Dose-related differential accumulation of morphine in specific regions of rat brain determined by mass fragmentography.

Regional morphine accumulation was examined in 8 brain areas (cerebral cortex, hippocampus, striatum, midbrain, hypothalamus, thalamus, medulla oblongata and cerebellum) following either a single dose or incremental doses administered by intraperitoneal injection. Morphine levels were determined by gas chromatography-mass spectrometry with chemical ionization detection. Prior to morphine assay, the vasculature was cleared of blood by saline perfusion to eliminate distortion of tissue-morphine by blood-morphine. Results indicate a dose-dependent, differential accumulation of morphine in different brain regions following incremental morphine administration. Three distinct uptake profiles were obtained, with the cerebellum, hippocampus, medulla and cortex showing roughly linear accumulation the midbrain, striatum and thalamus showing nonlinear accumulation, and the hypothalamus showing significantly higher absolute morphine levels than any other brain region.

Animals↗
PubMed1987

Evidence of an immune system to brain communication axis that affects central opioid functions: muramyl peptides attenuate opiate withdrawal.

Muramyl peptides are metabolic breakdown products of bacterial cell walls formed in vivo by the reticuloendothelial system. These agents have a variety of immune modulatory and neuropharmacologic effects. It has previously been demonstrated that a variety of immune modifying agents can induce alterations in certain behaviors elicited by opiates. In the present study we investigate possible reciprocal interactions between muramyl dipeptides (MDPs) and central opioid systems using three different experimental models: (1) naloxone-precipitated withdrawal behavior in morphine-dependent rats; (2) the tail immersion assay for determination of morphine-induced antinociception and (3) rectal temperature measurement of the pyrogenic activity of MDP. It is shown that two derivatives of MDP attenuate the severity of naloxone-precipitated withdrawal and morphine-induced antinociception. In addition, it is demonstrated that the pyrogenic activity of a stearoyl derivative of MDP is altered by chronic morphine treatment. These findings suggest both novel neuropharmacologic properties of muramyl dipeptides, as well as demonstrate that yet another immune modifier interacts with centrally mediated opioid phenomena.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Participation of lymphoid cells in the withdrawal syndrome of opiate dependent rats.

Treatment of rats with 500 Rads whole-body ionizing irradiation prior to chronic administration of morphine reduced the severity of the naloxone induced withdrawal signs. In contrast, adoptive transfer of 2-6 X 10(8) lymphoid cells to irradiated rats prior to chronic morphine treatment completely restored the ability to manifest the withdrawal signs precipitated by naloxone. These observations offer the possibility that the immune system participates in opiate addiction.

Animals↗
PubMed1987

Irradiation exposure modulates central opioid functions.

Exposure to low doses of gamma irradiation results in the modification of both the antinociceptive properties of morphine and the severity of naloxone-precipitated withdrawal in morphine-dependent rats. To better define the interactions between gamma irradiation and these opiate-mediated phenomena, dose-response studies were undertaken of the effect of irradiation on morphine-induced antinociception, and on the naloxone-precipitated withdrawal syndrome of morphine-dependent rats. In addition, electrophysiologic studies were conducted in rats after irradiation exposure and morphine treatment correlating with the behavioral studies. The observations obtained demonstrated that the antinociceptive effects of morphine as well as naloxone-precipitated withdrawal were modified in a dose-dependent manner by irradiation exposure. In addition, irradiation-induced changes in the evoked responses obtained from four different brain regions demonstrated transient alterations in both baseline and morphine-treated responses that may reflect the alterations observed in the behavioral paradigms. These results suggest that the effects of irradiation on opiate activities resulted from physiologic alterations of central endogenous opioid systems due to alterations manifested within peripheral targets.

Animals↗
PubMed1987

Differential modification of morphine and methadone dependence by interferon alpha.

Subcutaneous implantation of a pellet of methadone was presented as a novel method for the establishment of physical dependence upon this agent and it was compared to (1) the state of physical dependence induced by multiple injections of methadone, administered over several days, and (2) the dependence established by injections of morphine and the implantation of a morphine pellet. Comparable signs of drug dependence were observed in rats treated with both morphine and methadone following the administration of the opiate antagonist naloxone. The administration of interferon-alpha significantly attenuated the severity of the withdrawal syndrome in dependent rats after chronic exposure to morphine and to a lesser extent after morphine and methadone in combination. In contrast, alpha interferon did not affect 6 of the 7 abstinence signs in animals dependent upon methadone alone. The observations suggest that the states of physical dependence upon morphine and methadone may be separate phenomena that involve different physiological mechanisms. Thus, interferon may be a useful adjunct in the treatment of subjects dependent upon morphine but not in those dependent on methadone.

Animals↗
PubMed1987

Evidence of neuro-immunologic interactions: cyclosporine modifies opiate withdrawal by effects on the brain and immune components.

The capacity of the immune system to participate in processes primarily considered to be central nervous system (CNS) phenomena has been suggested recently by several studies demonstrating the ability of various immune modifiers to attenuate opiate withdrawal severity. The present study demonstrates that within 2 h after injection, the immune modifier cyclosporine A (CsA) has the ability to attenuate the opiate withdrawal syndrome precipitated by naloxone in morphine-dependent animals. Furthermore, it is demonstrated that this effect of CsA can be adoptively transferred by splenic mononuclear cells from immune-modulated (CsA-treated) donors into morphine-dependent recipients. However, unlike direct injections of CsA, CsA-treated immune components require at least 24 h to achieve their full attenuating effect upon withdrawal severity. Since opiate withdrawal behavior is predominantly a CNS-mediated phenomenon, these observations suggest both direct effects of CsA on the brain as well as the participation of immune components in the opiate withdrawal syndrome. This finding lends further support to the hypothesis that immune components have the ability to modulate central nervous system activities in a neuro-immunologic axis of communication.

Animals↗
PubMed1987

Cyclophosphamide and cortisol reduce the severity of morphine withdrawal.

Cyclophosphamide and cortisol, two nonspecific immunomodulators, significantly reduced the behavioral indices of naloxone-precipitated withdrawal in morphine dependent rats. Each immunomodulator reduced the morphine abstinence syndrome when administered either prior to or after chronic morphine treatment. Morphine exerts numerous effects on all levels of the central nervous system with tolerance, physical dependence, and a withdrawal syndrome being characteristics of this drug class. It is suggested that the degree of opiate dependence is directly correlated with the intensity of the behavioral withdrawal signs. Therefore, success in modifying the abstinence syndrome may lead to a better understanding of the dynamics of opiate dependence. The results reported herein coupled with similar findings for alpha-interferon and cyclosporine, suggest that opiate dependence may involve the immune system.

Animals↗
PubMed1987

Single injection of three different preparations of alpha-interferon modifies morphine abstinence signs for a prolonged period.

Opiates exert numerous effects on all levels of the central nervous system, with tolerance and physical dependence (addiction) being characteristics of this drug class. The capacity of the immune system to participate in processes primarily considered to be central nervous system phenomena has been suggested recently by several studies demonstrating the ability of various immune-modifiers to attenuate opiate withdrawal severity. Therefore, the immunomodulator agent, interferon was investigated to determine the effect upon the opiate withdrawal signs in an animal model. The degree of morphine dependence is measured by quantifying the various behavioral signs associated with naloxone-induced withdrawal. Three different preparations of human alpha interferon (alpha-IFN) were investigated to determine the duration of their attenuating effect upon the naloxone-induced abstinence syndrome in morphine-addicted rats. All three preparations of alpha-IFN reduced the severity of the opiate withdrawal (i.e., addiction) signs for several weeks. There were differences in the potency and the duration of the effects among the three different preparations of alpha-IFN.

Animals↗
PubMed1986

The effect of alpha-interferon, cyclosporine A, and radiation-induced immune suppression on morphine-induced hypothermia and tolerance.

An interconnection between the immune and the central nervous systems has been suggested by investigators studying the actions of several types of immune modifying agents and procedures upon opiate related phenomena. These studies have included the effects of altering immune system function by administration of either alpha-interferon, cyclosporine or radiation exposure upon naloxone-precipitated opiate withdrawal and upon opioid antinociceptive effects. The present study extends these earlier investigations by examining the effect of immune modulation upon opiate induced hypothermia. The results demonstrate that interferon and cyclosporine have no effects on baseline temperature or morphine induced hypothermia, while irradiation exposure elicits hyperthermia without affecting morphine-induced hypothermia. Finally, neither cyclosporine nor irradiation affect the development of tolerance to morphine induced hypothermia, while a single injection of the immune system modifier interferon was able to prevent the development of such tolerance. These observations suggest that yet another opiate-related phenomenon may be regulated at least in part by the immune system. These results together with our previous findings are further evidence of a link between the immune system and the CNS mediated through the opioid system. In addition, these studies further support our earlier hypothesis that "Interferon" is one of the endogenous substances which serves to prevent the development of tolerance and dependence to endogenous opioids.

Animals↗
PubMed1986

Opiate antinociception is altered by immunemodification: the effect of interferon, cyclosporine and radiation-induced immune suppression upon acute and long-term morphine activity.

It has recently been demonstrated that various forms of immune modification result in a profound attenuation of the opiate withdrawal syndrome. Herein we investigate the extent to which some of the immune modifiers active in withdrawal attenuation affect other opiate related behaviors, namely antinociception and the development of tolerance to this effect. The observations demonstrate that immune modification by cyclosporine and irradiation exposure result in an alteration of the acute antinociceptive effect of morphine; while none of these treatments modify the development of tolerance to this property of morphine.

Animals↗
PubMed1986

The parafasciculus thalami as a site for mediating the antinociceptive response to GABAergic drugs.

Electrophysiological (single cell) experiments were undertaken to examine whether neurons in the rat parafasciculus thalami (PF) are involved in mediating the antinociceptive response to GABAergic drugs. The results indicated that: noxious stimuli excite most PF neurons; microiontophoretic application of morphine, GABA or the GABA agonist, THIP, attenuated the spontaneous firing rate of PF neurons; morphine, THIP and GABA reduced the neuronal excitation induced by noxious stimuli; application of the GABA receptor antagonist, bicuculline, prevented the effects of THIP and GABA on PF activity; while naloxone blocked the response to morphine on PF neurons, it failed to influence the actions of GABA and THIP; and the injection of THIP or GABA into the PF produced an antinociceptive response as assessed by the rat tail-immersion assay, whereas pentobarbital was inactive. The findings suggest that GABA receptors located in the PF may mediate the antinociceptive response to GABAergic drugs, and that the action of these agents is unrelated to opiate receptors.

Animals↗