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1.
The effect on the parameters of seizures of opiates, administered in doses used clinically for analgesic effects, was studied in rats with full amygdaloid-kindled seizures. The largest dose of fentanyl studied (100 micrograms/kg) had a pronounced inhibitory effect on kindled seizures: severity of seizures, duration of seizures and duration of afterdischarge were significantly reduced to 36, 40 and 37% of controls, respectively, and the latency of seizures was significantly increased to 168% of untreated animals. The largest dose of pentazocine (16 mg/kg) also significantly inhibited the duration of seizures and duration of afterdischarge. Morphine (1-4 mg/kg) and meperidine (4-16 mg/kg) had a tendency to inhibit the duration of seizure and afterdischarges but did not significantly affect any of the measured parameters of seizures. Fentanyl, meperidine and pentazocine resulted in a lowering, whereas morphine caused a slight elevation, of the threshold for initiation of kindled seizures. The data suggest that fentanyl, in relatively small doses, may cause an inhibition of the intensity of behavioural and electrographic seizures but, paradoxically, an increased sensitivity to induction of seizures in rats with full amygdaloid-kindled seizures.  相似文献   

2.
Seizures were kindled in the amygdala and ventral hippocampus of rats until a stage 5 (clonic convulsion) was elicited. Stage 5 thresholds were then determined. Animals were then injected with either saline, or a 600 mg/kg, or 1600 mg/kg dose of 25% ethanol. The effect of each of these injections on seizure thresholds was assessed. The 1600 mg/kg dose caused a significant elevation in both AD and motor seizure thresholds, relative to the 600 mg/kg dose and saline, which did not differ. The elevation of seizure thresholds was significantly greater for animals with seizures kindled in the ventral hippocampus.  相似文献   

3.
Cysteamine suppresses kindled seizures in pentylenetetrazol-kindled rats   总被引:1,自引:0,他引:1  
Rats were kindled by intraperitoneal injection of pentylenetetrazol (PTZ) (30 mg/kg) every 48 h. Once kindled, animals received a single injection of cysteamine (200 mg/kg) and subsequent responses to PTZ were observed. Cysteamine, an agent which depletes brain somatostatin and suppresses kindled seizures in amygdaloid-kindled rats, markedly suppressed the severity of PTZ-induced seizures in PTZ-kindled rats as well. However, it did not alter the convulsive response of non-kindled rats to a submaximal convulsive dose (50 mg/kg) of PTZ. The results support a role for somatostatin in kindling.  相似文献   

4.
Previous studies have shown that methylxanthines such as aminophylline increase the clinical severity and length of electrically elicited limbic afterdischarges in naive and kindled rats without lowering seizure threshold. When fully amygdaloid-kindled rats are electrically stimulated at intertrial stimulation intervals of less than 60 minutes, significant residual inhibition can be demonstrated. The present study examines the effect of three doses of aminophylline (25, 50 and 100 mg/kg) on repeated daily stimulations of fully amygdaloid-kindled rats. After 100 mg/kg aminophylline, the first elicited amygdaloid-kindled seizure afterdischarge was doubled in length compared to saline controls. The second elicited seizure 15 minutes later resulted in status epilepticus and hindlimb extension in the majority of the aminophylline-treated animals with death occurring in 28%. When 25 or 50 mg/kg of aminophylline was given daily for five days before the first of five daily stimulation trials, each separated by 15 minutes, no significant reduction in postictal inhibition was demonstrated compared to saline controls. The 50 mg/kg aminophylline dose consistently and significantly lengthened only the first afterdischarge of each day without affecting the postictal inhibition seen with repeated stimulations. The neural substrate that governs immediate postictal inhibition of amygdaloid-kindled seizures appears to be resistant to modification by aminophylline at low doses. At high doses of aminophylline (100 mg/kg), sustained epileptical activity occurred. The sustained seizure activity seen at the high dose of aminophylline may be secondary to blockade of the processes which normally terminate seizure activity, or it may represent actual inhibition of the immediate postictal inhibitory processes.  相似文献   

5.
The effect of a glycine derivative (CP 1552-S) on kindled seizures in rats   总被引:1,自引:0,他引:1  
The effects of the glycine derivative, CP 1552-S (2-N-pentylaminoacetamide hydrochloride) were evaluated for potential anticonvulsant activity in rats which were cortically- or amygdaloid-kindled. Large doses (300-600 mg/kg, i.p.) of CP 1552 given 30 min before stimulation resulted in significant reductions in duration of afterdischarge after both partially-developed and fully-developed cortically-kindled seizures. The largest dose tested (600 mg/kg, i.p.) markedly reduced the duration of the elicited afterdischarge and the severity of seizure. This dose was associated with prestimulation sedation and a 50% incidence of post-afterdischarge spontaneous, electrical seizure activity. Against kindled amygdaloid seizures, CP 1552-S significantly reduced the duration of afterdischarge at 300 mg/kg (i.p.) without modifying the seizure and without prestimulation behavioral or electrical effects. The largest dose tested (600 mg/kg, i.p.) resulted in a significant reduction of the elicited duration of afterdischarge but was associated with a 25% incidence of prestimulation spontaneous electrical seizure activity and a 45% incidence of post-afterdischarge electrical seizure activity. When CP 1552-S (30-300 mg/kg, i.p.) was administered daily, prior to the amygdaloid kindling stimulus, no difference was noted in the rate of acquisition of the kindled amygdaloid response. It is concluded that the glycine derivative CP 1552-S, has little anticonvulsant activity against the acquisition or development of kindled amygdaloid seizures. It appears to have significant anticonvulsant effects against both cortically- and amygdaloid-kindled afterdischarges with little effect on the behavioral severity of the seizure. Further, large doses of CP 1552-S appeared to result in paradoxical post-afterdischarge and possibly prestimulation electrical seizure activity.  相似文献   

6.
Summary Memantine (1-amino-3,5-dimethyladamantane) has previously been shown to attenuate or block chemically or electrically induced seizures in rodents at doses of 5–20 mg/kg i.p., suggesting that the drug might have potential utility in the treatment of seizures. In the present study, the effects of memantine were examined in amygdala-kindled and non-kindled rats. In fully kindled rats, i.e. a model of focal seizures with secondary generalization, memantine exerted no effects on seizure parameters at 5 mg/kg i.p., but reduced seizure severity and duration at 10 mg/kg. The threshold for induction of afterdischarges recorded from the amygdala was not altered after administration of 10 mg/kg. At 20 mg/kg, memantine induced spontaneous motor seizures in amygdala-kindled rats. No motor seizures were observed in non-kindled rats, but in both kindled and non-kindled animals memantine, 20 mg/kg, induced spikes in the electroencephalogram. Additional dose-dependent behavioural alterations observed after memantine included hyperactivity, ataxia and stereotypies, which may relate to the dopaminomimetic properties of the drug. The results demonstrate that kindled rats are more sensitive to central nervous system stimulating effects of memantine than non-kindled rats, which could relate to an impairment of inhibitory processes and/or alterations in synaptic transmission mediated by excitatory amino acids in the kindled brain. Send offprint requests to W. Löscher at the above address  相似文献   

7.
To investigate the role of endogenous opioids on ventilatory control in pentobarbitone-anesthetized rats, the opioid antagonists naloxone and naltrexone were studied for their effects on ventilation, arterial blood gases and on ventilatory responses to hypoxia and carbon dioxide. In animals breathing room air, intravenous administration of naloxone and naltrexone (4 and 10 mg/kg) caused a dose-related increase in tidal volume, respiratory rate and minute volume. These ventilatory responses were rapid in onset and were associated with a decrease in arterial PaCO2, an increase in arterial pH and an increase in arterial PaO2. Intravenous naloxone (4 mg/kg) antagonized the increase in PaCO2 and decrease in arterial pH induced by the administration of morphine (3 mg/kg, i.v.). In animals breathing 100% O2, intravenous administration of naloxone and naltrexone (4 and 10 mg/kg) did not stimulate ventilation. Furthermore, intracerebroventricular administration of naloxone (15 and 150 micrograms) had no measurable effect on ventilation. Ventilatory responses to both hypoxia and carbon dioxide were not augmented by intravenous naloxone (4 mg/kg) and naltrexone (4 and 10 mg/kg). In fact, the increase in respiratory rate due to hypoxia was significantly (p less than 0.05) reduced by naltrexone (10 mg/kg, i.v.). In conclusion, our results demonstrate that naloxone and naltrexone caused hyperventilation in pentobarbitone-anesthetized rats. This effect was probably triggered by stimulation of the peripheral arterial chemoreceptors and did not involve mechanisms directly associated with the central nervous system. However, endogenous opioids were not involved in the chemical control of breathing in pentobarbitone-anesthetized rats since ventilatory responses to hypoxia and carbon dioxide were not changed by administration of these opioid antagonists.  相似文献   

8.
Voltage-sensitive calcium (VSC) channels may contribute to epileptogenesis. A systematic examination of the anticonvulsant efficacy of different classes of VSC channel inhibitors, however, is lacking in chronic seizure models. The present study evaluated representatives from three different classes of VSC channel inhibitors for their protection against amygdala kindled seizures. Adult male rats (n=12) were kindled to stage 5 seizures (GS), and a threshold intensity required to evoke a GS was determined. The Ca++-channel inhibitors (verapamil 0, 10, 20, 40 mg/kg; nimodipine 0, 5, 25, 50 mg/kg; nitrendipine 0, 25, 50, 100 mg/kg and flunarizine 0, 20, 40, 80 mg/kg) were administered 60–90 min prior to amygdala stimulation at the established threshold. None of the drugs altered threshold for inducing a seizure. Verapamil, a phenylalkylamine, and the dihydropyridines nimodipine and nitrendipine were without effect on kindled seizures. The diphenylalkylamine, flunarizine, was found to be the most efficacious, reducing AD duration and duration of clonic seizure activity by more than 60% in most animals. Flunarizine also decreased the severity of behavioral seizures, with 40% of the animals displaying Stage 1–2 seizures only. It is concluded that some VSC Ca++-channel inhibitors do possess anticonvulsant potential. Thus influx of extracellular calcium through VSC channels may contribute to the expression of kindled seizures.Although the research described in this article has been supported by the United States Environmental Protection Agency (through contract 68-02-4450 to Mantech Environmental Technology Incorp.), it has not been subjected to Agency review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred. Mention of tradenames or commercial products does not constitute endorsement or recommendation for use.  相似文献   

9.
Voltage-dependent calcium channel-blockers were studied for their ability to modulate limbic seizures induced in rats by injection of quinolinic acid and kainic acid into the hippocampus or by hippocampal kindling. Flunarizine, at 40 mg/kg (but not 20 mg/kg), reduced the total number of seizures and total time spent in seizures induced by quinolinic acid by 75%; at 60 mg/kg, both parameters were reduced more than 90%, while at 80 mg/kg seizures induced by kainic acid were not affected. Forty and 60 mg/kg of flunarizine protected hippocampal-kindled rats from fully developed convulsions (Stage 5). Nifedipine, at 20 and 40 mg/kg, was ineffective on seizures induced by both quinolinate and kainate. However, at 20 mg/kg, 57% of the kindled animals were protected from Stage 5 and total protection was achieved at 40 mg/kg. Verapamil, at 40 mg/kg, reduced by respectively, 88% and 78%, the total number of seizures and the total time spent in seizures induced by quinolinic acid, but had no effect on seizures induced by kainate and Stage 5 seizures. The results suggest that, while seizures induced by kainic acid were refractory to all voltage-dependent calcium channel blockers, binding sites affected by flunarizine and verapamil in the brain may selectively facilitate ictal activity induced by quinolinic acid. Binding sites for dihydropyridine might contribute to the increased hippocampal excitability in kindled animals. The role of calcium entry through voltage-dependent calcium channels in the occurrence of seizures in these models of limbic epilepsy is discussed.  相似文献   

10.
The purpose of the present study was to investigate whether prenatal exposure to morphine has effects on excitatory amino acid-induced seizures. Adult male rats, exposed on embryonic days 11-18 to saline or morphine, were injected with N-methyl-D-aspartate (NMDA) (150, 175, 200, 225, and 250 mg/kg) or kainic acid (KA) (15 or 20 mg/kg) in adulthood to assess the occurrence and latency to onset of stereotypy and seizures. The latency to onset of stereotypy was significantly increased after 175 mg/kg, and decreased after 200 mg/kg of NMDA in morphine-exposed animals. The lowest dose of NMDA (150 mg/kg) induced seizures in prenatally saline-treated control male rats but not in the morphine-exposed male rats. In the KA-injected group, prenatally morphine-exposed males had shorter latency to onset of wet-dog shakes, but there were no effects on the latency to onset of clonic seizures. The data suggest that prenatal morphine exposure has long-term effects on seizure susceptibility and the onset of stereotypy in the excitatory amino acid-induced seizure models.  相似文献   

11.
The development of tolerance to therapeutic effects of antiepileptic drugs can be a problem in the treatment of epilepsy, bipolar disorder, and pain syndromes. In the present study, acute treatment with the new antiepileptic drug lamotrigine (LTG, 15 mg/kg) markedly suppressed seizure stage and seizure duration in amygdala-kindled rats; but this antiseizure effect was rapidly lost following 4-8 days of repeated treatment. When gabapentin (GBP, 20 mg/kg) was coadministered with LTG, the ability of LTG to suppress seizure stage, seizure duration, and after-discharge (AD) duration was markedly extended. In addition, GBP coadministration with LTG decreased the number of animals that developed LTG-related running fits (Stage 6 seizures) and lengthened the number of days required to develop running fits or complete tolerance. Neither acute nor repeated treatment with MK-801 (0.3 mg/kg), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, had effects on kindled seizures. However, cotreatment with MK-801 markedly extended the anticonvulsant effects of LTG on the three seizure indices and reduced running fits. These data indicate that cotreatment with either GBP or MK-801 slows tolerance development to the anticonvulsant effects of LTG on kindled seizures. Therapeutic implications of the present study remain to be explored.  相似文献   

12.
Anticonvulsant role of adenosine   总被引:1,自引:0,他引:1  
The effects of 2-chloroadenosine (2-CLA), a metabolically stable analog of adenosine, and aminophylline, an adenosine receptor antagonist, on seizures produced by pilocarpine (PILO) were examined in rats. The effects of 2-CLA on amygdaloid and hippocampal kindled seimres were also examined. In the animals pretreated with aminophylline (25-100 mg/kg), a non-convulsant dose of PILO (100 mg/kg) resulted in severe motor limbic seizures which rapidly evolved to status epilepticus. 2-CLA (5-10 mg/kg) blocked the appearance of behavioral and EEG seizures produced by a convulsant dose of PILO (380 mg/kg) and completely blocked the evolution of hippocampal and amygdaloid kindled seizures. The results indicate that purinergic mechanisms are involved in the modulation of seizure threshold within the limbic system.  相似文献   

13.
The effects of various doses of diazepam (0.5–4 mg/kg) and phenobarbital (7.5–60 mg/kg) were determined on prekindled and kindled amygdaloid seizures in the same rats. Diazepam was ineffective against the prekindled focal seizures, but demonstrated profound and statistically significant control of the kindled seizures. In the kindled state, diazepam reduced the afterdischarge duration and seizure rank score to prekindled levels. Only the largest sedating dose of phenobarbital produced a reduction of both prekindled afterdischarge duration and seizure rank score. Against the kindled seizure, phenobarbital showed a marked and statistically significant increase in effectiveness in all but the smallest dose tested. The afterdischarge duration of kindled seizures was reduced to prekindled levels by 15–60 mg/kg of phenobarbital, while seizure rank score was reduced to prekindled levels by 30 and 60 mg/kg phenobarbital. The effects of two doses of diazepam (0.5 and 2.5 mg/kg) and phenobarbital (7.5 and 30 mg/kg) were tested against prekindled and kindled pentylenetetrazol (PTZ)-induced seizures. Preliminary work with 3 doses of pentylenetetrazol (30, 40 and 60 mg/kg) demonstrated that repeated doses of 30 mg/kg readily kindled seizures without the significant mortality seen with larger doses. Both diazepam and phenobarbital were less effective against seizures kindled with 30 mg/kg pentylenetetrazol compared to prekindled seizures. The comparative lack of effect that was seen with diazepam and phenobarbital against the pentylenetetrazol kindled seizure at doses associated with control of the kindled amygdaloid seizure may reflect an underlying difference in the pathogenesis of kindling between these seizure models. Further, the lack of suppression of the prekindled amygdaloid afterdischarge duration by large doses of diazepam, in contrast to large doses of phenobarbital, may also reflect differences between the mechanisms of action of these two drugs. This paradigm provides a model for testing the effectiveness of anticonvulsants during the progressive development of various epileptogenic seizures.  相似文献   

14.
Modification of the rate of acquisition of the kindled amygdaloid seizure by the convulsants pentylenetetrazol, bicuculline and strychnine was studied. Injections of saline, 25 mg/kg of pentylenetetrazol, 2 mg/kg of bicuculline or 1 mg/kg of strychnine were given 15 min prior to the daily electrical stimulation of the amygdala. The drug doses selected were capable of producing some behavioral and electrical epileptoid activity prior to stimulation without inducing generalized seizures. To determine whether pentylenetetrazol or bicuculline accelerated the rate of development of the kindled amygdaloid seizure or merely augmented the expression of each seizure, a crossover design was implemented. The crossover studies involved switching animals during the acquisition phase (between stimulations 3–6) from prestimulation saline to drug or drug to saline injections. It was found that pentylenetetrazol markedly augmented the expression of seizures during kindling development but the results of the crossover studies showed a less dramatic acceleration in the actual rate of the development of the fully generalized kindled amygdaloid seizure. The bicuculline-treated animals showed little augmentation in the expression of seizures during the kindling acquisition phase and in the actual rate of development of the kindled amygdaloid seizure. The strychnine treated animals showed no augmentation in expression of the seizures nor in the rate of development. The effects of prestimulation injections of bicuculline (1, 2 and 3 mg/kg) and strychnine (0.5, 1 and 2 mg/kg) on fully developed kindled amygdaloid seizures were also evaluated. Pretreatment with bicuculline minimally increased seizure afterdischarge duration at the highest dose. When fully kindled animals were pretreated with strychnine, a paradoxical decrease in afterdischarge length and an increase in severity (tonic hindlimb extension) was seen with the largest dose tested. This study emphasizes the potential importance of crossover studies in evaluating pharmacological manipulations of the rate of acquisition of the kindled seizure.  相似文献   

15.
The effects of various doses of diazepam (0.5–4 mg/kg) and phenobarbital (15–60 mg/kg) were determined on prekindled (focal) and kindled (generalized) cortical seizures in the same rats. Only high sedating doses of diazepam or phenobarbital reduced the elicited afterdischarge duration (ADD) and behavioral response in the prekindled focal cortical seizure. Against the kindled seizure, both diazepam and phenobarbital showed a marked and statistically significant increase in effectiveness in all but the smallest doses tested. The ADD of the kindled cortical seizures was reduced to prekindled lengths by diazepam (1–4 mg/kg) or phenobarbital (30–60 mg/kg). The increased anticonvulsant effectiveness found in this study is similar to previous findings with diazepam and phenobarbital against prekindled and kindled amygdaloid seizures, but stands in contrast to findings with prekindled and kindled pentylenetetrazol seizures.  相似文献   

16.
Morphine-induced analgesia, and the development of morphine-induced tolerance and dependence was determined in mice which had drunk caffeinated water (1 mg/ml) for 14 days or in mice which had received (-)-N6-(phenylisopropyl)-adenosine (PIA) 1 mg/kg i.p. for 14 days. Analgesia was assessed by the tail flick assay. The development of dependence was assessed by determining the ED50 of naloxone to precipitate withdrawal jumping (3 h after 100 mg/kg morphine pretreatment or 72 h after s.c. implantation of a morphine 75 mg pellet) and by determining the extent of naloxone-precipitated hypothermia in morphine-implanted animals. In mice chronically administered caffeine, the ED50 for morphine-induced analgesia was significantly decreased while the naloxone ED50 for withdrawal jumping increased by 2-fold after both types of morphine pretreatment. In control animals (tap water for 14 days), doses of 1 and 10 mg/kg of naloxone caused significant hypothermia in morphine-implanted animals. Doses of naloxone up to 100 mg/kg did not cause significant hypothermia in morphine-implanted animals which had received chronic caffeine. The development of tolerance was determined by computing the morphine potency ratio for the tail flick assay (tolerant ED50/control ED50). In mice chronically administered caffeine, the potency ratio was decreased significantly in morphine-implanted animals when compared to control. Morphine-induced analgesia, tolerance and dependence was not changed significantly in animals chronically administered PIA. Neither the distribution of morphine to the brain nor the opioid receptor binding parameters for [3H]etorphine and [3H]naltrexone were altered in mice chronically administered caffeine or PIA.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

17.
The effects of morphine on body temperature were studied in rats in two different states - stressed and non-stressed. Morphine injected subcutaneously (s.c.) produced a dual action on body temperature in non-stressed rats. Hyperthermia occurred at lower doses (2.5-10 mg/kg) while hypothermia was produced with a higher dose (20 mg/kg). Both of these effects of morphine were reversed by naloxone (0.1-5.0 mg/kg). Stressing the rats (immobilization with wire mesh) produced slight hypothermia which was markedly potentiated by morphine (5-20 mg/kg) in a dose-dependent manner. Enhancement of hypothermia by morphine in the stressed animals was antagonized by pretreatment with naloxone (0.1-5.0 mg/kg). When rats were treated with morphine (10 mg/kg) 1 h before stress, and were then exposed to immobilization stress, the hyperthermia exhibited in the non-stressed state changed to hypothermia in the stressed state. When the rats which were treated with morphine and then stressed for 1 h were released from stress, the hypothermia observed in the stressed state progressively changed to hyperthermia. Furthermore, these morphine effects, i.e. hyper- and hypothermia in the non-stressed and stressed states, respectively, were reversed but not eliminated by naloxone. These results suggest that the effects of morphine on core temperature in rats are altered depending upon the state of the animals. That is, morphine appears to have a dual action, hyperthermia in the non-stressed state and hypothermia in the stressed state. It also appears that these actions are mediated via opiate receptors.  相似文献   

18.
The present experiment was designed to examine whether the acute sensitization to naltrexone that is induced by a single dose of morphine could be blocked by pretreatment with naloxone. Food-deprived male Sprague-Dawley rats were trained to respond for food on a multiple-trial fixed interval 3-min schedule. Reinforcement was contingent upon a response within a 10-s limited hold period following a fixed interval of 3 min. A trial consisted of three fixed intervals separated by a 10-min timeout period during which responses were not reinforced. The rate decreasing effects of the opioid antagonist naltrexone were determined by cumulative dosing. Pretreatment with morphine (3.0 mg/kg, SC) resulted in a 70-fold increase in sensitivity to the response rate decreasing effect of naltrexone compared with saline pretreatment. The increased sensitivity was dose-dependently blocked by naloxone administration 10 min before morphine. The blockade by naloxone was overcome by increasing the pretreatment dose of morphine to 10 mg/kg. The results provide further evidence that acute agonist-induced sensitization to the rate-reducing effects of naltrexone is mediated by opioid receptors.  相似文献   

19.
Abstinence from chronic morphine results in characteristic withdrawal symptoms in humans and experimental animals. Despite a large number of studies, the cellular mechanisms underlying opiate withdrawal symptoms are not clearly understood, in particular, the regulation of micro-opioid receptor function during this process. The present study investigated the micro-opioid receptor-stimulated G-protein activity using guanylyl 5'-[gamma-[35S]thio]-triphosphate ([35S]-GTPgammaS) autoradiography. [35S]-GTPgammaS binding was performed using coronal rat brain sections (20 microm) in the presence or absence of the micro-opioid selective agonist [D-Ala(2),N-MePhe(4)Gly(5)-ol] enkephalin (DAMGO). In experiment 1, rats (male, Sprague-Dawley) were injected every 12 h with increasing doses of morphine (5-100 mg/kg, s.c.) for 12 days; a separate group of rats which received saline injections served as control. Opiate withdrawal was induced by abstinence from morphine. Thirty-six hours after the last morphine injection, spontaneous withdrawal symptoms were assessed. Rats were then decapitated and brains rapidly removed. In experiment 2, withdrawal symptoms were precipitated with the opioid receptor antagonist naloxone (1 mg/kg). Brains were taken at 5, 10, 20 and 60 min after naloxone injection. In experiment 3, morphine dependence was induced by implantation of three morphine pellets (75 mg per pellet). After 7 days, withdrawal symptoms were precipitated by naloxone (1 mg/kg) and brains were removed 30 min after naloxone injection. [35S]-GTPgammaS binding was measured in the locus coeruleus, nucleus parabrachialis, nucleus accumbens and central nucleus of amygdala. Although clear withdrawal symptoms were observed in all morphine-withdrawn rats, no significant changes in [35S]-GTPgammaS binding were detected in animals undergoing withdrawal. The present lack of differences between morphine-withdrawn and control rats indicates that micro-opioid receptor-stimulated G-protein activity is not modulated by chronic morphine administration and is not involved in the expression of opiate withdrawal.  相似文献   

20.
The anticonvulsant effectiveness of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 were evaluated against threshold and suprathreshold (400 microA) stimulation in fully amygdaloid-kindled rats. Pretreatment with either RO 15-1788 (3, 10 and 30 mg/kg), CGS-8216 (3, 10 and 30 mg/kg) or PK-11195 (10 and 60 mg/kg) failed in this study to modify consistently either the afterdischarge thresholds or elicited suprathreshold seizures or duration of afterdischarge. Using a double injection paradigm, the effectiveness of these three benzodiazepine antagonists to reverse the anti-convulsant and behavioral effects of diazepam were studied. When diazepam (3 mg/kg) was injected 15 min before or after a second injection of the vehicle control DMSO (0.25 ml/kg), a significant reduction in the duration of afterdischarge and seizure rank, elicited by a suprathreshold stimulation in amygdaloid-kindled rats, occurred. When either CGS 8216 (10 mg/kg) or RO 15-1788 (10 mg/kg) were given 15 min before diazepam (3 mg/kg) prior to stimulation, the anticonvulsant properties of diazepam were blocked. When RO 15-1788 (10 mg/kg) was given 15 min after diazepam, antagonism of the anticonvulsant effects on diazepam was shown. However, when either CGS-8216 (10 mg/kg) or PK-11195 (10 and 60 mg/kg) were given 15 min after diazepam (3 mg/kg), the anticonvulsant properties of diazepam were not blocked. The anticonvulsant effects of diazepam were reversed when CGS-8216 (10 mg/kg) was given 5 min after diazepam (3 mg/kg) or when a larger dose (30 mg/kg) was given at the same 15 min interval.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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