Biomedical subjects

N Dafny

Publications and source records attributed to N Dafny.

At least 55 records · Page 3Linked to original sources

PubMed1996

Sequential mediation of norepinephrine-and dopamine-induced antinociception at the spinal level: involvement of different local neuroactive substances.

The effects of intrathecally (i.t.) administered opioid antagonist naloxone (Nal), adenosine antagonist aminophylline (Aph), and gamma-aminobutyric acid (GABAA)-receptor antagonist picrotoxin (PTX) or Bicuculline (BIC) on the antinociception produced by i.t. norepinephrine (NE), dopamine (DA), morphine (Mor), 5'-N-ethylcarboxamidoadenosine (NECA, an adenosine agonist) or muscimol (MUS, a selective GABAA-receptor agonist) were studied and compared using the tail-flick test in rats. The results showed that: (1) both i.t. NE (0.3, 0.5 and 1.0 nmol) and DA (5.5, 8.3 and 16.5 nmol) produced significant and dose-dependent increases in tail-flick latencies (antinociception); (2) both Nal (240 nmol) and Aph (120 nmol) blocked the antinociception produced by NE (1.0 nmol); (3) both Nal (240 nmol) and Aph (120 nmol) blocked the antinociception produced by Mor (0.5 nmol), but only Aph (120 nmol) blocked the antinociception produced by NECA (0.5 nmol), while Nal (240 nmol) did not; (4) neither Nal (240 nmol) nor Aph (120 nmol) altered the antinociception produced by DA (16.5 nmol); (5) both i.t. PTX (1.5 nmol) and BIC (0.5 nmol) completely blocked the antinociception produced by DA (16.5 nmol), but showed no effects on that produced by NE (1.0 nmol); and (6) both PTX and BIC blocked the antinociception produced by MUS (1.0 nmol). These results suggest that: (a) endogenous opiate and adenosine may be involved in the mediation of NE-induced, but not DA-induced, antinociception; (b) NE, opioid and adenosine may act in a sequential order in NE-induced antinociception at the spinal level; (c) endogenous GABA may be involved in the mediation of DA-induced antinociception through the GABAA-receptors, but is not involved in NE-induced antinociception at the spinal level.

Animals↗

PubMed1995

Adenosine and opiate-like substances mediates antinociception at the spinal cord.

The effects of intrathecally administered naloxone or aminophylline on the antinociception produced by intrathecal NE, 5-HT, morphine or adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA) were observed in rats using the tail-flick test. The results show that: (1) the antinociception produced by NE with doses of 0.5 or 1.0 nmol could be completely blocked by both naloxone (240 nmol) and aminophylline (120 nmol); (2) neither naloxone (240 nmol) nor aminophylline (120 nmol) could alter the antinociception produced by 5-HT with doses of 60 or 120 nmol; and (3) the antinociception produced by morphine (0.5 nmol) could be blocked by both naloxone (240 nmol) and aminophylline (120 nmol), while the antinociception by NECA (0.5 nmol) could be blocked only by aminophylline (120 nmol), but not by naloxone (240 nmol). The results suggest that opiate-like substances (OLS) and adenosine are involved in the mediation of the NE-produced antinociception, but not in 5-HT-produced antinociception. Results also suggest that NE, OLS and adenosine may act in a sequential order in the performance of NE-induced antinociception at the spinal level.

Adenosine↗

PubMed1995

Monocular visual deprivation at the critical period modulates photic evoked responses.

Photic evoked responses were recorded from the striate cortex of Long-Evans hooded normal (control) rats and from monocular visual deprivation (MD) rats. The averaged visual evoked responses (AVER) were obtained from both hemispheres and provide comparison between the contralateral and the ipsilateral striate cortex with relation to the monocular deprived eye. The AVER recorded following binocular photic stimulation after 1 month of monocular deprivation demonstrated that the two visual cortexes responded differently. In the contralateral hemisphere of the visual cortex (related to the MD eye), all three components (P2, N2 and P3) of the AVER of the MD rats had significant increases in their peak amplitude as compared to the control recordings. In the ipsilateral cortex, the amplitude of component P2 and N2 was significantly reduced as a result of 1 month of MD. Comparing the AVER amplitudes of the two homotopic sites of the visual cortex obtained from the control group reveals no differences between the two hemispheres but markedly significant differences in P2, N2 and P3 components for the MD group. Based on the literature, the possibility that the monocular visual deprivation at the critical period in early developmental stage modulates the AVER as a result from the neurocytological alteration from altering of GABA and ACh within the striate cortex was discussed. In conclusion, the AVER is a reliable and practical method for studying the effects of monocular deprivation and neuroplasticity in the rat visual cortex.

Animals↗

PubMed1995

Interaction of serotonin and norepinephrine in spinal antinociception.

The interactions between different doses of serotonin (5-HT) and norepinephrine (NE) in in vivo experiments on rat spinal cord dorsal horn cells was investigated using the integrated electromyography (EMG) measurement of the nociceptive hindlimb flexor reflex (FR). The results indicate that (1) intrathecal (IT) administration of low doses of 5-HT (60 nmol) or NE (1.5 nmol) suppresses the nociceptive FR by 40% for 20 min, respectively; (2) administration of higher doses of 5-HT (240 nmol, IT) multiplies the suppression of the nociceptive FR by 80% for 40 min, and NE (15 nmol, IT) produces similar suppression of the nociceptive FR for 80 min; (3) concomitant administration of low doses of 5-HT (60 nmol, IT) and NE (1.5 nmol, IT) produces a summation of the nociceptive FR suppression both in amplitude and duration; (4) concomitant administration of the higher doses of 5-HT (240 nmol IT) with NE (15 nmol, IT) produces similar effect obtained as 5-HT given separately, and no summation was obtained as observed following the lower dosages; (5) serotonin (240 nmol, IT) given 40 min before NE (15 nmol, IT) attenuates the duration of the suppression induced by NE; (6) pretreatment with a selective 5-HT2 receptor antagonist ketanserin (60 nmol, IT) failed to abolish the 5-HT effects; (7) pretreatment with ketanserin prior to concomitant administration of the higher doses of 5-HT and NE prolongs the time duration of the nociceptive FR suppression.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1995

Visual deprivation at the critical period modulates photic evoked responses.

Average visual evoked responses (AVER) were recorded from the striate cortex of normal (control) and monocular visually deprived Long-Evans hooded rats. One month of monocular visual deprivation (MD) at the critical period of development resulted in marked reduction of all the three AVER components (i.e., components P2, N2 and P3) as compared to the control recording (P < 0.001). In control animals, the AVER amplitudes of the two hemispheres were identical, while in MD rats, the P2 and N2 components of the AVER obtained from the hemisphere ipsilateral to the MD eye were markedly smaller than those of the AVER obtained from the contralateral hemisphere (P < 0.001). The latencies of the late components (N2 and P3) obtained from the hemisphere ipsilateral to the MD eyes were significantly delayed as compared to those from the contralateral hemisphere (P < 0.05 for N2, P < 0.01 for P3). The AVER following paired photic stimuli with various time intervals between the stimuli were used to study the neuronal recovery function of control animals compared to MD animals. The AVER to the second stimulus obtained from the MD rats exhibited greater attenuation in their amplitude responses than the AVER obtained from the control group, i.e., slower neuronal recovery. The neurophysiological changes observed in this study may relate to the neurocytological alteration occurring in the striate cortex following monocular visual deprivation at the critical period. In conclusion, AVER recorded from monocular visually deprived rats during the critical period is a simple and reliable electrophysiological animal model to study neuroplasticity during postnatal development.

Animals↗

PubMed1994

Morphine and norepinephrine-induced antinociception at the spinal level is mediated by adenosine.

The purpose of this study was to examine whether adenosine or serotonin is involved in mediation of the antinociception produced by norepinephrine at the spinal cord level. Aminophylline, an adenosine receptor antagonist and naloxone given intrathecally (i.t.) were used to test the antinociception produced by i.t. norepinephrine, serotonin, morphine or the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) by using the tail-flick assay in rats. It was observed that (1) aminophylline blocked the antinociception produced by norepinephrine, but exhibited no effect on the antinociception produced by serotonin, (2) aminophylline blocked the antinociception produced by morphine similarly to naloxone, (3) aminophylline blocked the antinociception produced by NECA and (4) naloxone failed to block the antinociception produced by NECA and serotonin. The results suggest that adenosine is involved in mediation of the norepinephrine-produced antinociception at the spinal level and that norepinephrine and adenosine may act in a sequential manner in norepinephrine-induced antinociception.

Adenosine↗

PubMed1994

Alpha-interferon suppresses food intake and neuronal activity of the lateral hypothalamus.

Alpha-interferon (alpha-IFN) treatment in humans induces anorexic effects. However, the mechanisms and sites of action are unknown. Rats implanted with an intracerebroventricular (i.c.v.) cannula for local injection, and semi-microelectrodes in the lateral hypothalamic (LH) area for neuronal recording were used. The animals were kept in metabolic cages, and food and water intake was measured daily at 7:00 and 19:00 hr for 35 days, including: 5 days before the experiment; 10 days during daily alpha-IFN application (either i.p. 1500 I.U./gbw, or i.c.v. 1500 and 150 I.U./animal) and/or a vehicle control group; and 20 days post drug treatment. The unitary activity recording from the LH area was made before (30 min), during (10 min) and after (200 min) the alpha-IFN applications. alpha-IFN elicited a reversible dose-related decrease of both food intake and body weight. This decrease in food intake following alpha-IFN injections was correlated with a depression of LH neuronal electrical activity. Since direct brain application (i.c.v.) and systemic (i.p.) alpha-IFN treatment elicited identical responses, it is possible to assume that alpha-IFN suppresses food intake by a direct action on CNS sites including the LH neurons.

Animals↗

PubMed1994

Norepinephrine and serotonin-induced antinociception are blocked by naloxone with different dosages.

The effects of intrathecally (IT) administered naloxone (Nal) on the antinociception produced by IT norepinephrine (NE), serotonin (5-HT), or morphine (Mor) were observed and compared in rats using the tail-flick (TF) assay. The results show that: a) NE, 5-HT, and Mor in doses of 1 nmol, 240 nmol, and 0.5 nmol, respectively, produce similar increases in amplitude and time in TF latency (TFL); b) Nal treatment of 240 and 360 nmol has no effects on TFL; c) the antinociception produced by NE (1 nmol) can be blocked by Nal (240 nmol); d) antinociception produced by Mor (0.5 nmol) can also be blocked by Nal (240 nmol); e) 240 nmol of Nal does not affect the 5-HT (120 nmol)-produced antinociception, while 360 nmol of Nal show a delayed blockade to the 5-HT (120 nmol)-produced antinociception. The results suggest that endogenous opiate-like substances may be involved in both NE- or 5-HT-produced antinociception at the spinal level, and these effects may be mediated through different types of opiate receptors.

Animals↗

PubMed1994

SNF9007: a novel analgesic that acts simultaneously at delta 1, delta 2 and mu opioid receptors.

Intracerebroventricular administration of the synthetic cholecystokinin analog SNF9007 (Asp-Tyr-D-Phe-Gly-Trp-[NMe]-Nle-Asp-Phe-NH2) produced antinociception in the mouse hot-plate and warm water tail-flick tests. The mechanisms of its analgesic actions were assessed by administering antagonists selective for CCK (cholecystokinin octapeptide, sulfated)-A and CCK-B receptors, as well as specific antagonists for the mu opioid receptor (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, 1 microgram i.c.v.), the delta-1 opioid receptor [D-Ala2-Leu5,Cys6]enkephalin, 4.57 nmol i.c.v., 24 hr pretreatment), the delta-2 opioid receptor (naltrindole benzofuran, 25 pmol i.c.v.) and the kappa opioid receptor (nor-binaltorphimine, 10 mg/kg s.c.). The antinociceptive activity of SNF9007 was not a result of the activation of CCK receptors, as treatment with either CCK-A or CCK-B receptor antagonist was ineffective in blocking SNF9007 antinociception. Nor-binaltorphimine and naltrindole benzofuran were completely ineffective in blocking SNF9007 antinociception when administered alone or in combination. However, co-administration of delta-1 or delta-2 opioid receptor antagonists with the mu opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 resulted in a dramatic reduction in analgesic responses to SNF9007. Furthermore, the co-administration of mu+delta-1 + delta-2 opioid receptor antagonists resulted in an even greater inhibition of SNF9007 antinociception (> 10-fold shift). We conclude that SNF9007 acts simultaneously at brain delta-1, delta-2 and mu opioid receptors to induce antinociceptive effects in mice.

Amino Acid Sequence↗

PubMed1993

Muscarinic receptors mediate the effect of acetylcholine (ACh) on neurons of the bed nucleus of the stria terminalis (BNST).

This study was designed to determine the type of receptor mediating the effect of ACh on BNST neurons. 45% of BNST neurons showed a dose-dependent monophasic increase in firing rate in response to ACh. Muscarinic antagonist blocked the effects of ACh. Amygdala stimulation (Amyg S) elicited excitatory responses, but atropine and hexamethonium had no effect on the Amyg S induced excitation. The experiment shows that the excitatory effect of ACh on BNST neurons is mediated by muscarinic receptors, while the excitatory effects of Amyg S on BNST neurons is not mediated by ACh.

Acetylcholine↗

PubMed1993

Responses of neurons in bed nucleus of the stria terminalis to microiontophoretically applied morphine, norepinephrine and acetylcholine.

The bed nucleus of the stria terminalis is a basal forebrain nucleus that receives inputs from limbic system nuclei and sends projections to several hypothalamic and brainstem nuclei, proposed to be involved in the physiological response to stressors. The bed nucleus of the stria terminalis also receives norepinephrine- (NE), acetylcholine- (ACh) and opiate-containing projections. The objectives of this experiment were to examine the effects of microiontophoretically applied ACh, NE and morphine sulfate (M) on neurons of the bed nucleus in urethane-anesthetized rats and to determine the degree to which these systems interact on individual neurons. Acetylcholine was excitatory in 43% of the neurons and NE was inhibitory in 70%. Morphine however, elicited two distinct types of response--excitation in 24% of the neurons and inhibition in 28%. Each of these effects was current-dependent and monophasic. Since 77% of neurons of the bed nucleus responded to two or more of the drugs used in this experiment, statistical analysis was used to determine correlations between responses to each of these drugs. This analysis showed that neurons that responded to M with excitation also responded to ACh with excitation, while neurons that responded to M with inhibition, were nonresponsive to ACh. No correlation was found between NE and either M or ACh. Thus, this experiment demonstrated the possible effects of noradrenergic, cholinergic and opioid innervation on firing rates of neurons of the bed nucleus of the stria terminalis and may explain the roles these neurotransmitters play in modulating the response to stress.

Acetylcholine↗

PubMed1993

Cerebellar stimulation modulates thalamic noxious-evoked responses.

Parafascicular (PF) neurons responding to noxious stimuli and focal electrical stimulation of midbrain, diencephalon, and hypothalamic nuclei, which send projections to PF, modulates the PF spontaneous and noxious-evoked responses. Some cerebellar efferents ascend to PF. This investigation attempted to study the effect of cerebellar stimulation on spontaneous and noxious-evoked PF neuronal activity in rats. It was observed that 26% (73/280) of PF neurons responded to a noxious stimulus. The PF neuronal population exhibits two cell types according to their response pattern following the noxious stimulus. One type of PF neurons were excited (n = 53) and were classified as nociceptive-on cells. The second type of PF neurons responded to noxious stimulus by a decrease in the ongoing firing rate (n = 20) and were classified as nociceptive-off cells. The responses of these two types of nociceptively identified cells were tested following cerebellar lateral nucleus stimulation (Lat.N.S.) utilizing several current intensities. Lat.N.S. with lower intensities (0.1-0.2 mA) elicited suppression of both spontaneous and nociceptive-evoked discharges of the nociceptive-on neurons, although higher intensities (0.4-0.6 mA) elicited excitation on both discharges of this type of neuron. In contrast, Lat.N.S. induced a monophasic intensity-dependent suppression of both the spontaneous and the nociceptive-evoked discharges of the nociceptive-off neurons. The results indicate that Lat.N.S. modulates the nociceptive-evoked responses of PF neurons. The possible role and related pathways of cerebellum in modulating noxious input were discussed.

Animals↗

PubMed1993

Noninvasive subthreshold auricular electrical stimulation reduces the severity of precipitated and abrupt opiate withdrawal.

The objective of this study was to use noninvasive, subthreshold auricular electrical stimulation (AES) as a treatment to reduce the severity of precipitated and of abrupt opiate withdrawal. Sixty-four male Sprague-Dawley rats were divided into six groups. The first three groups were used to study the effects of AES on naloxone-precipitated withdrawal; the other three groups were used to examine the influence of AES on abrupt withdrawal. Morphine dependence was induced by multiple injections of the drug on an incremental staircase dosage regimen for 6 days. The results obtained from first three groups show that AES reduced the severity of the withdrawal signs precipitated by naloxone injection (0.5 mg/kg SC) by more than 75% (p < 0.01). The observations obtained from the other three groups show that AES reduced the severity of abrupt withdrawal for at least 4 h as assessed by measuring the locomotor behavior of the animals. This study demonstrates that noninvasive subthreshold AES is effective in reducing the severity of precipitated and of abrupt opiate withdrawal.

Animals↗

PubMed1992

Suppression of nociceptive responses in parafascicular neurons by stimulation of substantia nigra: an analysis of related inhibitory pathways.

A total of 166 neurons in parafascicular nucleus (PF) were studied, 85 from intact animals, 72 following dorsal spinal cord transection (D.Sp.C.X.), and 9 following complete transection of the spinal cord. Two patterns of nociceptive responses were identified following noxious stimulation and these responses were classified as 'nociceptive-on' and 'nociceptive-off' neurons, respectively. The effects of stimulating the substantia nigra (SNS) on the spontaneous and on the nociceptive evoked discharges were observed and compared in intact, D.Sp.C.X. and completely transected spinal cord rats. The results show that SNS significantly suppresses both the spontaneous and the nociceptive evoked discharges elicited by peroneal nerve stimulation. With an intact spinal cord, SNS suppressed both the spontaneous [-37 +/- 3.2% (P less than 0.05)] and the nociceptive evoked discharges [-52.8 +/- 2.8% (P less than 0.01)] of the 'nociceptive-on' cells respectively, while in the 'nociceptive-off' cells the same stimulation elicited an even more prominent suppression upon both discharges (-47.7 +/- 5.4%, P less than 0.01 and -64.9 +/- 5.0%, P less than 0.01), respectively. After D.Sp.C.X., the suppressive effects on the 'nociceptive-on' cells following SNS were diminished (-28.1 +/- 3.5% and -36.9 +/- 2.6%, respectively) but not abolished, while in the 'nociceptive-off' cells, the inhibitory effects on SNS were unchanged. In addition, the suppressive effects of SNS on the spontaneous activity of PF neurons in cases with completely cut spinal cords remains unchanged. These results suggest that SNS modulates the spontaneous and the noxious evoked responses of the PF neurons by way of supraspinal connections besides the previously described descending projecting pathways.

Action Potentials↗

PubMed1992

Evidence for two different afferent pathways carrying stress-related information (noxious and amygdala stimulation) to the bed nucleus of the stria terminalis.

The bed nucleus of the stria terminalis (BNST) is an important nucleus involved in mediating amygdala-regulated endocrine effects. Since the amygdala is important in mediating the endocrine response to noxious somatosensory stimuli and olfactory stimulation, this experiment studies whether noxious input (tail pinch, TP) and stress-related input (amygdala stimulation, AmygS) will modulate BNST neuronal activity. One hundred and fifty-eight BNST neurons were studied following AmygS, TP and cutaneous stroke. AmygS was effective in 66% of BNST neurons and produced one of the following five responses: oligosynaptic excitation (43%), polysynaptic excitation (5%), time-locked inhibition (4%), generalized increase in firing rate (8%), or generalized decrease in firing rate (6%). TP produced an increase in firing rate in 27% of BNST neurons tested. Analysis of a contingency table constructed to determine the degree of correspondence between neurons responsive to AmygS and neurons responsive to TP showed that the distributions of reactivity to these stimuli in BNST neurons are independent of each other. This suggests that although AmygS and TP are both capable of altering the firing rate of BNST neurons, the pathways by which they reach BNST differ.

Afferent Pathways↗

PubMed1992

D2 dopamine receptor involvement in spinal dopamine-produced antinociception.

Experiments were performed on 79 lightly pentobarbital-anesthetized rats. Rats displayed a dose-dependent increase in tail-flick latencies following the injection of dopamine (DA) into the lumbar subarachnoid space through an intrathecal tube. Sulpiride, a D2-subtype receptor antagonist, antagonized the DA-induced analgesia (antinociceptive) effect; while SCH-23390, a D1-subtype receptor antagonist, had no effect even in a higher dose. To further investigate whether the well-known spinal serotonergic, noradrenergic and opioidergic receptor systems were involved in DA-induced antinociception, their antagonists, methysergide, phentolamine, and naloxone were tested respectively. The results showed that phentolamine, but not methysergide or naloxone, could block the DA-induced antinociception. The present data provide evidence that DA exerts antinociceptive effects through D2-subtype dopamine receptor(s) at the spinal level, and that spinal alpha-adrenergic receptors may mediate this effect.

Animals↗

PubMed1992

Hypothalamic, dorsal raphe and external electrical stimulation modulate noxious evoked responses of habenula neurons.

Extracellular recording techniques were used to investigate the effects of focal brain stimulation and external electrical stimulation on spontaneous activity and on noxious evoked responses in the habenular nucleus of anesthetized Sprague-Dawley rats. Two hundred and forty-one habenular neurons were tested to noxious and non-noxious stimuli. The habenular neurons exhibited three cell types according to their patterns of response to the noxious stimulus: 123 neurons (51%) responded to noxious stimulus by excitation and were classified as "nociceptive-on" cells; 56 neurons (23%) responded to the same noxious stimulus by decreasing their firing rate and were classified as "nociceptive-off" cells; and 62 neurons (26%) failed to respond to noxious stimulation and were classified as "non-nociceptive" cells. None of these 241 cells responded to non-noxious stimulus. One hundred and fifty-five, 160, 142 and 241 habenular neurons were tested following focal lateral hypothalamus stimulation, dorsal raphe stimulation, cerebellar stimulation and transcranial electrical stimulation alone and concomitant with noxious stimulation, respectively. The observations demonstrate that focal lateral hypothalamic, dorsal raphe and external (transcranial) electrical stimulation suppresses habenular noxious evoked responses while cerebellar electrical stimulation elicits no effect on the nociceptive-off cells and augmenting effects on the nociceptive-on cells. In addition, it was observed that low current (below threshold) external transcranial electrical stimulation was as effective in suppression of habenular noxious evoked responses as was focal brain electrical stimulation in the lateral hypothalamus and dorsal raphe.

Acoustic Stimulation↗

PubMed1991

Restraint and stimulation of bed nucleus of the stria terminalis produce similar stress-like behaviors.

Restraint stress, electrical stimulation of the bed nucleus of the stria terminalis (BNST), and the combination of restraint stress and BNST stimulation were studied using a computerized animal activity monitoring system. Both restraint and the combination of restraint and BNST stimulation produced increases in locomotor, exploratory and stereotypic activity all of which returned to baseline within an hour while BNST stimulation alone also increased measurements of locomotor and exploratory behavior some of which remained elevated throughout the three-hour period of measurement. BNST stimulation also produced vigorous escape behavior and biting which were not seen with restraint alone. Thus electrical stimulation of BNST produces behavior which is qualitatively similar to the behavior produced by stress but differs in time course.

Animals↗