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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opioid agonists were used to investigate the modulation of seizures in the seizure-susceptible El mouse. Morphine and D-Ala2-D-Leu5-enkephalin (DADLE) were injected subcutaneously or intracisternally as prototypic agonists for mu and delta opioid receptors. Systemic or intracisternal injection of both morphine and DADLE decreased the incidence of seizures and the seizure score in El mice in a dose-dependent manner. The anticonvulsant effects of morphine and DADLE were reversed by naloxone (2 mg/kg, s.c.). This implies that opioid agonists have anticonvulsant properties which are mediated by mu and delta opioid receptors. In conclusion, a deficit in endogenous opioid peptides, which act as anticonvulsants may play a significant role in the etiology or pathophysiology of seizures in the El mouse.
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PMID:Effects of morphine and D-Ala2-D-Leu5-enkephalin in the seizure-susceptible El mouse. 132 4

Male Fischer-344 rats were given a single intrastriatal injection of kainic acid (KA; 1 microgram/rat), which caused recurrent motor seizures lasting 3-6 hr. During the convulsive period, native Met5-enkephalin-like (ME-LI) and dynorphin A (1-8)-like (DYN-LI) immunoreactivities in hippocampus decreased by 31 and 63%, respectively. By 24 hr after dosing, the hippocampal opioid peptides had returned to control levels, and by 48 hr ME-LI had increased 270% and DYN-LI 150%. Immunocytochemical analysis revealed that ME-LI and Leu5-enkephalin-like (LE-LI) immunostaining in the mossy fibers of dentate granule cells and the perforant-temporoammonic pathway had decreased visibly by 6 hr and had increased markedly by 48 hr following KA. A visible decrease in DYN-LI in mossy fiber axons within 6 hr was followed by a substantial increase by 48 hr. To determine whether the increases in hippocampal ME-LI reflected changes in ME biosynthesis, levels of mRNA coding for preproenkephalin (mRNAenk) and cryptic ME-LI cleaved by enzyme digestion from preproenkephalin were measured. Following the convulsive period (6 hr), mRNAenk was 400% of control, and by 24 hr, cryptic ME-LI was 300% of control. Increases in native and cryptic ME-LI and in mRNAenk were also noted in entorhinal cortex, but not in hypothalamus or uninjected striatum. Our data suggest that KA-induced seizures cause an increase in ME release, followed by a compensatory increase in ME biosynthesis in the hippocampus and entorhinal cortex.
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PMID:Kainic acid alters the metabolism of Met5-enkephalin and the level of dynorphin A in the rat hippocampus. 287 67

Radioimmunochemistry (RIA) and immunocytochemistry (ICC) were used to measure proenkephalin and prodynorphin peptides in the brain of a genetic model of epilepsy, the seizure-sensitive (SS) Mongolian gerbil. Brain levels of both [Met5]- or [Leu5]-enkephalin (ME-LI) and dynorphin A1-8 and dynorphin A1-17 (DN-LI) like immunoreactivity were increased in the hippocampal region of the SS gerbil. However, ME-LI and DN-LI did not follow the same patterns. ME-LI was significantly increased in the SS gerbils (post-seizure) compared to SR gerbils while ME-LI in SS (preseizure) gerbils was not significantly different from SR gerbils. DN-LI was significantly increased in the hippocampal region of both SS (preseizure) and SS (postseizure) gerbils compared to SR gerbils. These results strongly imply differences in the regulation of proenkephalin and prodynorphin metabolism in the Mongolian gerbil. The differences in metabolic regulation may signal fundamentally different roles of these opioid peptides in the modulation of seizure activity in this animal.
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PMID:Increased enkephalin and dynorphin immunoreactivity in the hippocampus of seizure sensitive Mongolian gerbils. 288 Jun 44

Kainic acid (KA), an excitatory neurotoxin, was used as a tool to study the metabolism of hippocampal opioid peptides and their functional role in the expression of wet-dog shakes (WDS). A single intracerebral injection of KA (1 microgram/rat) caused recurrent motor seizures lasting 3-6 h. During the convulsive period, native Met5-enkephalin-like (ME-LI) and dynorphin A(1-8)-like (DYN-LI) immunoreactivities in hippocampus decreased by 31 and 63%, respectively. By 24 h after dosing, the hippocampal opioid peptides had returned to control levels, and by 48 h ME-LI had increased 270% and DYN-LI 150%. Immunocytochemical analysis revealed that ME-LI and Leu5-enkephalin-like (LE-LI) immunostaining in the mossy fibers of dentate granule cells and the perforant-temporoammonic pathway had decreased visibly by 6 h and had increased markedly by 48 h following KA. A visible decrease in DYN-LI in mossy fiber axons within 6 h was followed by a substantial increase at 48 h. To determine whether the increases in hippocampal ME-LI reflected changes in ME biosynthesis, levels of mRNA coding for preproenkephalin (mRNAenk) and cryptic ME-LI cleaved by enzyme digestion from preproenkephalin were measured. Following the convulsive period (6 h), mRNAenk was 400% of control, and by 24 h, cryptic ME-LI was 300% of control. Increases in native and cryptic ME-LI and in mRNAenk were also noted in entorhinal cortex, but not in hypothalamus or uninjected striatum. Our data suggest that KA-induced seizures cause an increase in ME release, followed by a compensatory increase in ME biosynthesis in the hippocampus and entorhinal cortex. Several lines of evidence from this study have suggested that hippocampal enkephalins are intimately related to KA-elicited WDS. The shaking behavior was attenuated by pretreatment with naloxone or antisera against [Met5]-enkephalin. We also observed that KA-induced WDS can be mimicked by intrahippocampal injection of enkephalin-related peptides. Furthermore, this study demonstrated that intact dentate granule cells are essential for KA- and enkephalin-induced WDS, since a colchicine injection into the ventral hippocampus, which selectively destroys granule cells, abolished this behavior.
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PMID:Kainic acid as a tool to study the regulation and function of opioid peptides in the hippocampus. 289 Feb 24

Blood flow, determined by the radioactive microsphere technique during epileptiform seizures induced by [D-Ser2,Leu5]enkephalyl-Thr (DSLET), a specific delta-opioid receptor agonist, was examined in different areas of the brain of the rat at various time intervals. An increase in blood flow to the hippocampus and brain stem was observed 2.5 min after administration of DSLET into the left lateral ventricle. An additional increase in flow occurred in the striatum and cerebellum 2.5 min later (5 min after the injection), at which time both the neural and vascular effects of the drug were most marked. Ten minutes after the administration of the drug, cerebral blood flow in all regions except the hippocampus, returned to the respective baseline values. Since the time-course and the magnitude of functional activity and blood flow in the hippocampus showed a good correlation, it is suggested that this region of the brain may play an essential role in triggering and maintaining the seizure phenomena induced by enkephalin.
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PMID:Regional cerebral blood flow during enkephalin-induced seizures in the rat. 301 98

Two groups of experiments were conducted to determine if morphine- and enkephalin-induced seizures are specifically mediated by the mu and delta receptor, respectively. In the first experiments, designed to assess the ontogeny of mu- or delta-seizures, rats from 6 h to 85 days of age received implanted cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. Various amounts of the mu-receptor agonists, morphine and morphiceptin, and the delta agonists, D-Ala2-D-Leu5-enkephalin (DADL) and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET), were then administered intracerebroventricularly (icv) with continuous EEG monitoring. The second experiments entailed use of the nonspecific opiate antagonist, naloxone, as well as the specific delta antagonist, ICI 154,129, against seizures induced by icv-administered morphine, morphiceptin, DADL, or DSLET. Both morphine and morphiceptin produced electrical seizure activity in rats as young as 5 days after birth. The drugs produced similar seizure activity in terms of electrical morphology, observed behavior, ontogeny, threshold dose, and reversibility with small doses of naloxone. In the pharmacologic experiments, icv naloxone blocked all opiate-induced seizures. ICI 154,129 blocked DSLET seizure, had little effect on enkephalin or DADL seizures, and no effect on morphine or morphiceptin seizures. These data indicate that DSLET seizures are delta-specific but that all other opiate-induced seizures studied may involve multiple opiate receptor-mediated mechanisms.
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PMID:Opiate-induced seizures: a study of mu and delta specific mechanisms. 301 59

Bilateral microinjections of DADL (D-Ala2-D-Leu5-enkephalin) and morphine were carried out in rats in a systematic fashion at histologically identified medial and lateral thalamic sites. DADL produced a dose-dependent (1.5-15.0 nmol), naloxone-reversible (1 mg/kg, i.p.) increase in the hot-plate (HP), tail-flick (TF) and catalepsy (CAT) response latencies with a predominance of activity occurring at lateral as opposed to medial thalamic sites. These effects were seen within 5 min of microinjection. At a significant number of sites, DADL precipitated convulsive seizure activity. Equimolar doses of morphine had a negligible effect on nociceptive indices and were not productive of seizures even at sites where DADL was found to be active. To further examine seizure activity, rats were prepared with bilateral frontal cortical electrodes and microinjected also at medial and lateral thalamic sites with equimolar doses of DADL and morphine (15 nmol). DADL was found to produce electrographically defined seizures unaccompanied by convulsive motor behavior (cataleptic seizures), as well as convulsive seizures. All animals in this group exhibiting analgesia and catalepsy had electrographic evidence of a seizure with markedly abnormal EEG tracings showing postictal spiking and changes in baseline frequency and amplitude. These seizures appeared to be naloxone-reversible. Morphine on the other hand was not productive of seizures, but did produce changes in electroencephalographic activity including spindle bursting, high-voltage slow-frequency activity as well as spiking. As noted, these changes were not associated with any effects on nociceptive measures.
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PMID:Studies on the effects of intrathalamically injected DADL and morphine on nociceptive thresholds and electroencephalographic activity: a thalamic delta receptor syndrome. 302 Dec 75

The opioid receptor types involved in the mediation of enkephalin-induced electroencephalographic (EEG) seizures were studied in unanesthetized, freely moving rats. Four receptor-selective peptide ligands were evaluated for effectiveness in producing nonconvulsive EEG seizures after i.c.v. administration; these included the mu agonist, [D-Ala2-N-methyl-Phe4-Gly5-ol]enkephalin (DAGO), the mixed mu-delta agonist, [D-Ala2-D-Leu5]enkephalin (DADLE), and the selective delta agonists, [D-Pen2-D-Pen5]enkephalin and [D-Pen2-L-Pen5]enkephalin. Only DAGO and DADLE were found to produce EEG seizures, with DAGO being 9 times more potent than DADLE. DAGO produced a greater number of seizure episodes with a greater overall incidence compared with DADLE, reflecting its potent effect to elicit EEG seizure activity in these rats. Injections of [D-Pen2-D-Pen5]enkephalin or [D-Pen2-L-Pen5]enkephalin, even at the highest doses tested, failed to produce seizure activity. Behaviorally, the DAGO and DADLE EEG seizures were nonconvulsive but were temporally associated with episodic bursts of wet-dog shakes. The enkephalin-induced responses were extremely sensitive to antagonism by naloxone and completely blocked by pretreatment with the irreversible mu antagonist beta-funaltrexamine. The selective delta opioid receptor antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH) was ineffective. The use of the most selective agonists and antagonists for mu and delta opioid receptors suggests that, in rats, enkephalin-induced EEG seizures are mediated exclusively by mu opioid receptors and not by delta opioid systems.
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PMID:Evidence for mu opioid receptor mediation of enkephalin-induced electroencephalographic seizures. 302 18

In rats the influence of the delta opioid agonists [Leu]enkephalin, [D-Ala2-D-Leu5]enkephalin, [D-Ala2]methionine enkephalinamide and synthetic analogue of [Met]enkephalin: Tyr-D-Ala-Gly-Phe-D-Leu-OMe on audiogenic seizures was tested during ethanol abstinence. All investigated drugs significantly inhibited this ethanol withdrawal symptom. The results are compatible with the hypothesis of opioid involvement in the ethanol abstinence syndrome.
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PMID:Audiogenic seizures during ethanol withdrawal can be blocked by a delta opioid agonist. 302 46

We examined the effect of opioid receptor antagonists on the seizure phenomena induced by specific delta opioid receptor agonist [D-Ser2,Leu5] enkephalyl-Thr (DSLET). The experiments have been performed in the anesthetized rats, and the DSLET-induced seizure phenomena were registered by electrocorticogram and electromyogram. It was demonstrated that two selective delta opioid receptor antagonists, ICI 152,129 and ICI 174,864 inhibited DSLET-induced epileptiform ECoG pattern and myoclonic contractions in a dose-related manner. An equimolar concentration of naloxone failed to antagonize the epileptiform effects of DSLET. It is concluded that delta opioid receptor agonist-induced seizure is mediated by delta receptors, since it can be blocked by delta opioid receptor antagonists. Evidently, delta opioid antagonists can be used as a good tool, in order to demonstrate a delta component in the seizure phenomena induced by other endogenous opioid peptides or their derivatives.
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PMID:Effects of delta opioid antagonists on enkephalin-induced seizures. 303 87


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