Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown that opioid peptide levels are altered in hippocampal formation of kindled animals. We therefore studied the distributions of mu and delta opioid binding sites in hippocampal formation of kindled and control rats using quantitative in vitro autoradiography. Animals received daily stimulations of the amygdala until they experienced 3 class 5 seizures. Paired control animals underwent implantation of electrodes but were not stimulated. Mu binding sites were labeled with 125I-FK-33824. Twenty-four hours after the last kindled seizure, mu binding was decreased by 32% in stratum pyramidale of CA1 and stratum radiatum of CA2 and by 17-27% throughout most of the rest of CA1, CA2, and CA3. Few, if any, differences were seen between kindled and control animals at 7 or 28 days after the last kindled seizure. Delta binding sites were labeled with 125I-[D-Ala2,D-Leu5]enkephalin in the presence of the morphiceptin analog PL-032. Twenty-four hours after the last kindled seizure, delta binding was decreased only in stratum moleculare of the dentate gyrus. Seven days after the last kindled seizure, delta binding was decreased by 11-17% throughout CA1, CA3, and the dentate gyrus. At 28 days after the last seizure, however, no differences were found between kindled and control animals. Since the decreases in mu and delta opioid binding are transient, they are unlikely to be the molecular basis of the permanent kindling phenomenon. Rather, these changes in opioid binding may represent responses to repeated seizures.
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PMID:An in vitro autoradiographic analysis of mu and delta opioid binding in the hippocampal formation of kindled rats. 303 68

Morphine hydrochloride (25-200 nmol), [D-Ala2, D-Leu5]enkephalin (10-200 nmol) and naloxone hydrochloride (100-1000 nmol) were injected unilaterally into the rat amygdala and the following electrographic, behavioural and neuropathological responses were studied. Microinjections of low doses of morphine (25-50 nmol) resulted in behavioural alterations characterized by staring, gustatory automatisms and wet shakes, whereas higher doses additionally produced motor limbic seizures and status epilepticus. The first changes in the electroencephalogram appeared in the amygdala immediately after the administration of morphine and rapidly spread to hippocampal and cortical areas. Electrographic alterations consisted of high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and periods of postictal depression. Neuropathological analysis of frontal forebrain sections by means of light microscopy revealed widespread, seizure-related damage confined to amygdala, olfactory cortex, thalamus, hippocampal formation, neocortex and substantia nigra. Pretreatment of animals with naloxone, 2-20 mg/kg s.c., as well as simultaneous microinjection of the non-convulsant dose of naloxone, 100 nmol, with morphine, 100 nmol, into the amygdala failed to block the development of convulsant activity and seizure-related brain damage produced by the opiate. In contrast, diazepam, 10 mg/kg i.p., when administered prior to the microinjection of morphine into the amygdala, abolished the epileptogenic effects of the drug. [D-Ala2, D-Leu5]Enkephalin, 10-200 nmol, elicited electrographic and behavioural responses similar to those seen after low doses of morphine, when administered into the amygdala. High voltage fast activity, single spikes, bursts of polyspiking, electrographic seizures and periods of postictal depression were seen in the electroencephalogram, but no behavioural signs of motor limbic seizures could be detected. The only behavioural correlates of epileptiform electrographic activity were wet shakes, myoclonic head twiches and gustatory automatisms. The examination of frontal forebrain sections from rats receiving [D-Ala2, D-Leu5]enkephalin revealed no morphological changes. Pretreatment of rats with either naloxone, 2 mg/kg, or diazepam, 10 mg/kg, blocked the development of behavioural and electrographic sequelae of the peptide. Naloxone, 100-1000 nmol, when microinjected into the amygdala, produced electrographic, behavioural and morphological alterations resembling those seen after high doses of morphine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Convulsant action of morphine, [D-Ala2, D-Leu5]-enkephalin and naloxone in the rat amygdala: electroencephalographic, morphological and behavioural sequelae. 329 87

DPDPE ([D-Pen2, D-Pen5]-Enkephalin) and DPLPE ([D-Pen2, L-Pen5]-Enkephalin) are conformationally-constrained cyclic analogs of enkephalin with high selectivity for delta opioid receptors. Intracerebroventricular (i.c.v.) administration of each analog acutely produces a complex EEG response in rats characterized by a dose-related increase in spectral power and HVSA (peak frequency of 5.0 Hz) during behavioral stupor, and a theta driving (5.25-8.0 Hz) associated with intense behavioral arousal. These effects were antagonized by high (10 mg/kg), but not low (1.0 mg/kg), doses of naloxone. Both analogs failed to cause EEG or convulsive seizures. In contrast, i.c.v. administration of DADLE ([D-Ala2, D-Leu5]-Enkephalin), an enkephalin analog with activity at both mu and delta binding sites, caused initial nonconvulsive EEG seizures followed by HVSA (3.0 Hz); theta driving was not evident. The incidence of the seizures was dose-related and antagonized by very low doses of naloxone (0.01-1.0 mg/kg). Collectively, the inability of DPDPE and DPLPE to cause seizure activity, and the marked sensitivity of DADLE-induced EEG seizures to naloxone, suggest that delta receptors are not directly responsible for DADLE-induced EEG seizure activity. Furthermore, these data implicate mu opioid receptors as the primary sites responsible for enkephalin-induced seizures.
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PMID:Electroencephalographic assessment of the role of delta receptors in opioid peptide - induced seizures. 609

Morphine, the prototype mu opiate receptor agonist, decreased the spontaneous and [D-Ala2]-Met-enkephalinamide (DALA)-induced myoclonic contractions (MC) of submandibular muscles in the anaesthetized rat. The proposed kappa receptor agonists ketocyclazocine, ethylketocyclazocine and bremazocine failed to induce MC. In addition, bremazocine inhibited the spontaneous and DALA induced MC. Cyclazocine, the so-called sigma opiate receptor agonist, had a weak potency in generation of MC, but without step dose response tendency. The most potent opioid peptide in inducing the MC and electrocortical (ECoG) epileptic pattern was the delta opiate receptor agonist [D-Ala2,D-Leu5]-enkephalin (DADL). All drugs were administered intraventricularly. The results indicate that myoclonic phenomena induced by DADL and probably by other endopioids are mediated by delta opiate receptors in the rat brain. It is suggested that the combined ECoG and EMG method used in this study offers an opportunity to define further the biological role of opiate receptors and to identify the potential delta opiate receptor acting drugs, which might provide a new approach to the therapy of some seizure disorders.
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PMID:Delta opiate receptors are involved in the endopioid-induced myoclonic contractions. 627 61

The effects of various opiate receptor agonists on the seizure threshold after an intravenous infusion of pentylenetetrazol were investigated in rats. The mu- and epsilon-receptor agonists, morphine (20-40 micrograms) and beta-endorphin (5-10 micrograms) show proconvulsant properties towards clonic and tonic seizures. The delta-receptor agonist (D-Ala2,D-Leu5-enkephalin, DADL 5-40 micrograms) and alpha-neoendorphin (20-40 micrograms) show pro- and anticonvulsant properties towards clonic and tonic seizures, respectively. Anticonvulsant properties of DADL are possibly due to its action on the spinal cord, since after the intrathecal injection this effect is still observed. Similarities between DADL and alpha-neoendorphin suggest that they may act through the same receptor. The kappa-receptor agonist dynorphin A (5-20 micrograms) and its degradation-resistant analogue D-Arg-dynorphin1-13 (10 micrograms) show significant anticonvulsant properties. Our present results suggest that the kappa-receptor agonist dynorphin may act physiologically as an endogenous anticonvulsant, in contrast to other opioid peptides.
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PMID:The effect of various opiate receptor agonists on the seizure threshold in the rat. Is dynorphin an endogenous anticonvulsant? 631 15

In an effort to identify delta-receptor-specific properties for opioid modulation of seizure activity, studies were conducted with ICI 154,129, a putative delta-receptor antagonist, in the rat flurothyl test. Rats were pretreated i.c.v. with ICI 154,129 (50 micrograms) which, at this dose, does not alter normal seizure thresholds. Mean seizure thresholds for control groups (i.c.v. saline) ranged between 323-349 sec. In this test, D-Ala2-D-Leu5 enkephalin (20 micrograms, i.c.v.), metkephamid (40 mg/kg, s.c.), and etorphine (20 micrograms/kg, s.c.) raised seizure thresholds by 117, 128, and 140% of control, respectively. Meperidine (25 mg/kg, s.c.) lowered seizure thresholds by 14% less than control. Pretreatment with ICI 154,129 failed to antagonize the proconvulsant action of meperidine or the anticonvulsant and behavioral depressant actions of etorphine. The increases in seizure threshold produced by DADL and metkephamid (two delta-directed ligands) were significantly attenuated by ICI 154,129. However, the DADL-induced wet-shakes, rigid immobility, and behavioral depression were insensitive to ICI 154,129. These data indicate that ICI 154,129 possesses delta-receptor antagonistic properties in this in vivo model of seizure activity. Furthermore, since only the changes in seizure threshold were antagonized, it may be inferred that opioid-induced behavioral depression and DADLE wet-shakes are not a function of delta-receptor activity.
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PMID:A selective role for delta-receptors in the regulation of opioid-induced changes in seizure threshold. 631 16

Acute i.c.v. administration of ICI 154,129 (100-600 micrograms), a delta-opioid receptor antagonist, raised the seizure threshold in a dose-related manner in rats exposed to flurothyl, a volatile convulsant. Pretreatment with naloxone or beta-funaltrexamine (beta-FNA) antagonized this effect. Lower doses of ICI 154,129 (12.5-50 micrograms), which did not influence seizure threshold, selectively antagonized the anticonvulsant action of [D-Ala2,D-Leu5]enkephalin (DADLE) in the same procedure. Consequently, it may be inferred that ICI 154,129 at high doses has mu-agonist and at low doses delta-antagonist properties in the rat flurothyl test.
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PMID:ICI 154,129, a delta-opioid receptor antagonist raises seizure threshold in rats. 632 Dec 7

Morphine, beta-endorphin and [D-Ala2, D-Leu5] enkephalin administered intracerebroventricularly exerted a protective effect on electroconvulsive shock (ECS)-induced seizures in mice. This effect was reversed by intraperitoneal injections of naltrexone. The role of mu and delta receptors in ECS-induced convulsions is discussed.
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PMID:Opioid antagonism of electroshock-induced seizures. 633 Jul 66

It has been reported that delta opioid agonists can have neuroprotective efficacy in the central nervous system. This study was conducted to test the hypothesis that a delta opioid receptor (DOR) agonist, [D-Ala2, D-Leu5] enkephalin (DADLE), can improve neuron survival against experimental forebrain ischemia in rats. Using male rats (n=125), intraperitoneal injection of DADLE (0, 0.25, 1, 4, 16 mg kg-1) was performed 30 min before ischemia. Ten minutes interval forebrain ischemia was provided by the bilateral carotid occlusion combined with hypotension (35 mm Hg) under isoflurane (1.5%) anesthesia. All animals were neurologically and histologically evaluated after a recovery period of 1 week. As histological evaluation, percentages of ischemic neurons in the CA1, CA3, dentate gyrus (DG) were measured. During the recovery period, 27 rats died because of apparent upper airway obstruction, seizure, or unidentified causes. There were no differences in the motor activity score among the groups. Ten minutes forebrain ischemia induced approximately 75, 20, and 10% neuronal death in the CA1, CA3, and DG, respectively. Any doses of DADLE did not attenuate neuronal injury in the hippocampus after ischemia. Pre-ischemic treatment of DORs agonism with DADLE did not provide any neuroprotection to the hippocampus in rats subjected to forebrain ischemia.
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PMID:Delta opioid receptors stimulation with [D-Ala2, D-Leu5] enkephalin does not provide neuroprotection in the hippocampus in rats subjected to forebrain ischemia. 1720 74


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