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

We have shown that morphine has an anticonvulsive effect against maximal electroconvulsive shock (MES) in mice, and this effect is antagonized by histamine H1-receptor antagonists. Brain histamine is localized both in neurons and in mast cells, and morphine is known to enhance the turnover of neuronal histamine and to release histamine from mast cells. In the present experiments, compound 48/80 was injected chronically (0.5 mg/kg on day 1, 1 mg/kg on day 2, 2 mg/kg on day 3, 3 mg/kg on day 4, and 4 mg/kg on day 5, twice daily, ip) to deplete mast cell contents. Morphine (0.001-10 mg/kg, ip; N = 20) produced a dose-dependent anticonvulsive effect against MES seizure in mice with non-depleted mast cells, whereas it did not exert any anticonvulsive effect in mice with depleted mast cells. These results indicate that morphine produces its anticonvulsive effect against maximal electroconvulsive shock in mice by liberating histamine from mast cells.
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PMID:Compound 48/80, a histamine-depleting agent, blocks the protective effect of morphine against electroconvulsive shock in mice. 1071 85

Bicuculline was used to investigate seizure susceptibility in pre- and peripubertal male and female rats exposed prenatally to morphine. Morphine-exposed males showed increased seizure susceptibility at prepubertal and decreased susceptibility at peripubertal ages. There was no difference in seizure susceptibility in morphine-exposed females at either age. Therefore, the present data suggest that males are more vulnerable than females to morphine-induced insults during prenatal brain development.
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PMID:Prenatal morphine exposure alters susceptibility to bicuculline seizures in a sex- and age-specific manner. 1083

1. Morphine is recommended by the World Health Organization as the drug of choice for the management of moderate to severe cancer pain. 2. Education of health professionals in the past decade has resulted in a large increase in the prescribing of opioids, such as morphine, and in the magnitude of the doses administered, resulting in an improvement in the quality of pain relief available for many cancer patients. 3. However, the reported incidence of neuroexcitatory side effects (allodynia, myoclonus, seizures) in patients administered large doses of systemic morphine or its structural analogue, hydromorphone (HMOR), has also increased. 4. Clinically, increasing the magnitude of the morphine or HMOR dose administered to patients already exhibiting neuroexcitatory opioid related side effects, results in an exacerbation rather than an attenuation of the excitatory behaviours. 5. In contrast, cessation of the opioid or rotation to a structurally dissimilar opioid (e.g. from morphine/HMOR to methadone or fentanyl), usually results in a restoration of analgesia and resolution of the neuroexcitatory opioid side effects over a period of hours to days. 6. To explain the clinical success of 'opioid rotation', it is essential to understand the in vivo metabolic fate of morphine and HMOR. 7. Following systemic administration, morphine and HMOR are metabolized primarily to the corresponding 3-glucuronide metabolites, morphine-3-glucuronide (M3G) and hydromorphone-3-glucuronide (H3G), which are not only devoid of analgesic activity but evoke a range of dose-dependent excitatory behaviours, including allodynia, myoclonus and seizures, following intracerebroventricular (i.c.v.) administration to rats. 8. Several studies have shown that, following chronic oral or subcutaneous morphine administration to patients with cancer pain, the cerebrospinal fluid (CSF) concentrations of M3G exceed those of morphine and morphine-6-glucuronide (analgesically active morphine metabolite) by approximately two- and five-fold, respectively. 9. These findings suggest that when the M3G concentration (or H3G by analogy) in the CSF exceeds the neuroexcitatory threshold, excitatory behaviours will be evoked in patients. 10. Thus, rotation of the opioid from morphine/HMOR to a structurally dissimilar opioid, such as methadone or fentanyl, will allow clearance of M3G/H3G from the patient central nervous system over hours to days, thereby producing a time-dependent resolution of the neuroexcitatory behaviours while maintaining analgesia with methadone or fentanyl.
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PMID:Neuroexcitatory effects of morphine and hydromorphone: evidence implicating the 3-glucuronide metabolites. 1087 11

Sprague-Dawley rats were trained in a three-choice drug discrimination task utilizing 5mg/kg chlordiazepoxide (CDP), saline (SAL), and 15mg/kg pentylenetetrazole (PTZ) as stimulus conditions. Generalization tests of the three training conditions resulted in exclusively injection-appropriate lever selection. Cross-generalization tests with PTZ or CDP resulted in dose-dependent lever selections confined to the training drug and SAL levers. Morphine and ethanol cross-generalization tests produced saline-appropriate responding, whereas cocaine and caffeine produced PTZ-appropriate responding at high doses. Tests conducted after concomitant administration of both training drugs demonstrated a reciprocal antagonism between the two drugs. More importantly, when the training dose of CDP was held constant and combined with increasing doses of PTZ, a shift from CDP- to PTZ-appropriate responding through a dose range of exclusive SAL-appropriate responding was demonstrated. Overt behavioral indices of seizure activity occurred at dose combinations that engendered only saline responding, but PTZ-appropriate responding did not correspond with the development of overt seizure episodes. These data suggest that the PTZ discriminative cue in the present three-choice paradigm is not primarily linked to its proconvulsant effects. The data are discussed in terms of an hypothesis in which the discriminable interoceptive cues for PTZ and CDP lie at opposite ends of a single continuum that has a neutral centroid, and this continuum more likely reflects an anxiolysis-anxiogenesis dimension than an anticonvulsant-seizure dimension.
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PMID:Cue dimensionality in the three-choice pentylenetetrazole-saline-chlordiazepoxide discrimination task. 1122 84

The inferior colliculus (IC) is a well known relay station for auditory pathways in the brainstem. Much evidence has implicated this structure as part of a brain system mediating aversive states, and changes in its functioning as responsible for the occurrence of audiogenic seizures. Rats were implanted with chemitrodes, devices which allow electrical stimulation and microinjections of drugs in the same brain sites. Stepwise increases in the intensity of electrical stimulation of the IC of rats placed inside a circular arena allowed the determination of thresholds for freezing and escape behavior. Morphine (10-40nmol) caused dose-dependent increases in both aversive thresholds. A systemic injection of naloxone reversed the effects of morphine on the centrally induced aversive responses. These data suggest that neural substrates controlling defensive behavior in this structure are under opioid inhibitory control. Higher doses of morphine (80nmol) induced a non-naloxone reversible fearful hyper activity. It is suggested that opioid mechanisms exert an inhibitory control on the neural substrates of aversion in the IC and that high doses of morphine microinjected into IC cause pro-aversive actions probably through non-opioid mechanisms.
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PMID:Opposite effects of low and high doses of morphine on neural substrates of aversion in the inferior colliculus. 1122 51

Nitric oxide (NO) and morphine have been coupled in many physiological as well as pathological processes. The present study examined the involvement of the L-arginine/NO pathway in the anticonvulsant properties of systemic morphine (2-30 mg/kg) against electroshock seizures (ECS) in mice. Morphine decreased the intensity of maximal electroshock seizures (MES) and increased the threshold for ECS. Neither the NOS substrate L-arginine (30, 60, and 100 mg/kg), the reversible nonspecific NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 3, 10, and 30 mg/kg), the irreversible specific inducible NOS inhibitor aminoguanidine (20, 50, and 100 mg/kg), nor the opioid receptor antagonist naloxone (0.1, 0.3, and 1 mg/kg) did alter per se the ECS threshold or the intensity of MES at doses used. However, both naloxone and L-NAME, but not aminoguanidine, inhibited the anticonvulsant effects of morphine (30 mg/kg) against ECS, while L-arginine potentiated the anticonvulsant effects of lower doses of morphine (2 or 10 mg/kg). Low doses of naloxone (0.1 or 0.3 mg/kg) or L-NAME (3 mg/kg), which did not alter morphine effect per se, showed additive anticonvulsant effects against MES. Thus, the L-arginine/NO pathway seems to play a role in the anticonvulsant properties of morphine against ECS and this mediation involves the constitutive, but not the inducible, form of nitric oxide synthase.
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PMID:Mediation of nitric oxide in inhibitory effect of morphine against electroshock-induced convulsions in mice. 1266 93

The aim of this study was to examine effects of i.p. injected Fentanyl (0.005 mg/kg) and Morphine (1 mg/kg) on local cerebral blood flow (ICBF) and tissue pO2 level in frontal-parietal area of the cortex and nucleus accumbens of the rat's brain. Either fentanyl or morphine injection resulted in significant increase of local blood flow in the n.accumbens and its decrease in frontal-parietal area of cortex. Measurement of oxygen partial pressure revealed the opposite (to ICBF) changes: a decrease in n.accumbens and its increase in cortical area of the brain. Analysis of this data and electrical activity recorded from both said structures allow to conclude that they are conditioned by respective changes in functional-metabolic activity induced by intraperitoneal injection either fentanyl or morphine: its suppression in frontal-parietal area of the cortex and development of seizure-like activity in the n.accumbens.
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PMID:[Effect of fentanyl and morphine on local blood flow and tissue oxygen tension in cortical frontal-parietal area and nucleus accumbens in albino rats]. 1285 8

The neurochemical mechanisms involved in post-ictal antinociception remain to be elucidated. Application of electroconvulsive shock (ECS) to rats results in post-ictal antinociception. The objective of this study was to identify endogenous substances that could participate in antinociception during post-ictal depression induced by ECS (70 mA, 60 Hz, 1 s). Antinociception was measured by the rat paw-pressure test, in which increased sensitivity is induced by intraplantar injection of carrageenan. This test proved to be efficient in detecting the electroshock-induced antinociception. Intense post-ictal antinociception was observed over a period of 30 min after the end of the seizure. It was used nonspecific opioid and specific vasopressin antagonists and the prolactin (PRL) release inhibitor to test the reversal of antinociception. Administration of naloxone (5, 7.5 and 10 mg/kg) blocked the post-ictal antinociception. The V(1) (125 microg/kg) and V(2) (250 microg/kg) vasopressin receptor antagonists ([beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1),O-Et-Tyr(2),Val(4),Arg(8)]-vasopressin and [adamantaneacetyl(1),O-Et-d-Tyr(2),Val(4),Abu(6),Arg(8,9)]-vasopressin) also inhibited the nociceptive response. The antinociception blockade was more intense after administration of the V(1) receptor antagonist. Bromocriptine (4, 8 and 12 mg/kg) was able to reverse antinociception behavior during the post-ictal period. Morphine (1, 2 and 4 mg/kg), vasopressin (12.5, 100 and 400 microg/kg) and prolactin (100, 200 and 400 microg/kg) administration promoted a higher nociceptive threshold. It was administered the three substances with their respective antagonists to verify the opioidergic pathway and vasopressin and prolactin release interactions, and as a positive control. We observed that the tested mediators were released in an independent manner, indicating no interference in which other.
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PMID:Involvement of prolactin, vasopressin and opioids in post-ictal antinociception induced by electroshock in rats. 1501 57

Alterations in the opioid system in the hippocampal formation and some of the possible functional consequences were investigated in adult male rats that were prenatally exposed to either saline or morphine (10 mg/kg twice daily on gestational days 11-18). In situ hybridization and Northern blots were used to measure proenkephalin and prodynorphin mRNA, and radioimmunoassays quantified proenkephalin- and prodynorphin-derived peptide levels in the dentate gyrus, CA3, and CA1 subfields of the hippocampal formation. Prenatal morphine exposure in male rats decreases proenkephalin and increases prodynorphin mRNA selectively in the granule cell layer of the dentate gyrus. Similarly, met-enkephalin peptide levels are decreased and dynorphin B peptide levels are increased in the dentate gyrus but not CA3 or CA1 of prenatally morphine-exposed males. In addition, there are decreases in dynorphin-derived peptides in the CA3 subfield. Receptor autoradiography revealed increases in the density of micro but not delta receptor labeling in discrete strata of specific hippocampal subfields in morphine-exposed males. Because alterations in the hippocampal opioid system suggest possible alterations in the excitability of the hippocampal formation, changes in opioid regulation of seizures were examined. Morphine exposure, however, does not alter the latency to onset or number of episodes of wet dog shakes or clonic seizures induced by infusion of 10 nmol [D-Ala2, MePhe4, Gly-ol5]enkephalin into the ventral hippocampal formation. Interestingly, a naloxone (5 mg/kg) injection 30 min before bicuculline administration reverses the increased latency to onset of clonic and tonic-clonic seizures in morphine-exposed males. Thus, the present study suggests that exposure of rats to morphine during early development alters the hippocampal opioid system, suggesting possible consequences for hippocampal-mediated functions.
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PMID:Field-specific changes in hippocampal opioid mRNA, peptides, and receptors due to prenatal morphine exposure in adult male rats. 1520 53

Recent demonstrations of the anticonvulsant properties of agmatine suggest it may be considered as a potential adjunct for protection against seizure. We investigated the possibility of an additive anticonvulsant effect between low doses of agmatine and morphine. The thresholds for the clonic seizures induced by the intravenous administration of gamma-aminobutyric acid (GABA)-antagonist, pentylenetetrazole (PTZ) were assessed in mice. Morphine at lower doses (1-3mg/kg) increased and at higher doses (30, 60 mg/kg) decreased the seizure threshold. Pretreatment with a per se non-effective dose of agmatine (1mg/kg) potentiated the anticonvulsant effect of morphine. The combination of subeffective doses of agmatine and morphine led to potent anticonvulsant effects. The pro-convulsant effect of morphine was attenuated by agmatine. Yohimbine with a dose (1mg/kg) incapable of affecting seizure threshold reversed the effect of agmatine on both anticonvulsant and pro-convulsant effects of morphine. These results suggest that agmatine potentiates the anticonvulsant effect of morphine and alpha 2-adrenoceptors may be involved in this effect.
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PMID:The synergistic anticonvulsant effect of agmatine and morphine: possible role of alpha 2-adrenoceptors. 1597 66


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