beta-endorphin and Seizures

Previous data indicate that intracerebroventricular administration of agonists for mu- and delta-opioid receptors induces limbic seizures in rats, but no data are reported in rabbits. We found that the mu- and delta-opioid peptides [D-Ala(2)-N,Me-Phe(4)-Gly(5)-ol]enkephalin (DAMGO), beta-endorphin and deltorphin II, induced EEG non-convulsive hippocampal seizures, and changes in hippocampal background EEG, physical parameters and overt behaviour after central administration. Dexamethasone pre-treatment prevented DAMGO-, deltorphin II- and beta-endorphin-induced seizures as well as changes in background EEG, physical parameters and overt behaviour induced by mu-opioid agonists. Dexamethasone antagonism on opioid action was blocked by pre-treatment with a protein synthesis inhibitor, cycloheximide or by the kappa-opioid antagonist nor-binaltorphimine. Our data suggest that dexamethasone influences opioid actions at mu- and delta-receptors via a protein synthesis mechanism involving kappa-opioid receptors.

Topics: Analgesics, Opioid; Animals; beta-Endorphin; Dexamethasone; Electroencephalography; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Glucocorticoids; Oligopeptides; Rabbits; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Seizures

The present study examines alterations in the cytoplasmic immunoreactivity of brain beta-endorphin, an endogenous opioid peptide regarded as the mediator of both euphoria and antinociceptive systems, in relation to toxicities due to cocaine and combined cocaine-ethanol. Beta-endorphin-immunoreactive cells were visualized and counted in adjacent sections from male rat brains at the level of the arcuate nucleus. In this region, cytoplasmic beta-endorphin immunoreactivity is prevalent. An intraperitoneal injection of cocaine (75 or 15 mg/kg) was given 15 min after an intraperitoneal injection of 3 g/kg ethanol or vehicle. With a fatally toxic dose (75 mg/kg) of cocaine, the number of neurons exhibiting cytoplasmic beta-endorphin immunoreactivity (immunoreactive nerve cells) was significantly increased immediately after the drug administration. Ethanol further enhanced the effects of both 15 and 75 mg/kg of cocaine. When the immunoreactivity was visually estimated by computer imaging analysis, lightly stained, weakly immunoreactive cells with photographic light absorption values greater than 50% were enhanced in the cocaine-ethanol groups compared to the cocaine only groups. Fatal toxicities were only observed in the groups treated with the high cocaine doses (75 mg/kg), with or without ethanol. In these groups, the number of strongly immunoreactive cells had increased significantly compared to the other groups. In the group treated with the high cocaine dose (75 mg/kg) plus ethanol, an increased frequency of late deaths that occurred over 1 h after the drug administration was observed, together with a decreased severity of cocaine-induced seizures and an early enhancement of weakly immunoreactive cells. Unlike the strongly immunoreactive cells, the weakly immunoreactive cells appeared to be continuously enhanced, based on an experiment examining beta-endorphin immunoreactivity at 24 h after an injection of 50 mg/kg cocaine.

Topics: Animals; beta-Endorphin; Brain; Cocaine; Drug Synergism; Ethanol; Immunohistochemistry; Male; Rats; Rats, Wistar; Seizures; Time Factors

The effects of some beta-endorphin fragments with neuroleptic-like properties, i.e., tau-endorphin, des-tyr1-tau-endorphin (DT tau E), desenkephalin-tau-endorphin (DE tau E), in comparison with the dopaminergic antagonist haloperidol,- were studied on the EEG and behavioral alterations induced by beta-endorphin in the rabbit. beta-Endorphin administered i.c.v. (5-30 nmol) induced EEG nonconvulsive limbic seizures as well as EEG background and behavioral alterations which were antagonized by naloxone administered i.v. (1-2 mg/kg). Haloperidol, tau-endorphin, DT tau E and DE tau E were unable to prevent beta-endorphin-induced alterations when injected in a single dose i.v. (25-50 micrograms/kg), 15 min before beta-endorphin. Subchronic i.v. administration of DT tau E or DE tau E (25 micrograms/kg/day) for 4 consecutive days prevented completely EEG limbic seizures as well as EEG background and behavioral alterations induced by i.c.v. beta-endorphin injected 15 min after the fourth dose; however, haloperidol (30 micrograms/kg/day) administered with the same schedule as DT tau E or DE tau E was able to prevent only EEG epileptiform and EEG background alterations induced by beta-endorphin. tau-Endorphin administered i.v. for 4 consecutive days (25 micrograms/kg/day) did not consistently influence any of the beta-endorphin effects. Our results show that DT tau E and DE tau E, which are devoid of opioid activity, exert a strong antagonism on ictal seizures as well as on other EEG alterations and behavioral alterations induced by beta-endorphin, and suggest that the antagonism shown by these drugs and by haloperidol on the EEG effects induced by beta-endorphin are exerted at least in part through an indirect action, i.e., an interaction with the dopaminergic system.

Topics: Animals; Behavior, Animal; beta-Endorphin; Electroencephalography; Endorphins; Haloperidol; Injections, Intraventricular; Male; Naloxone; Peptide Fragments; Rabbits; Seizures

A number of stimuli including acute footshock and electrically-induced seizures lead to release of beta-endorphin immunoreactivity from the anterior pituitary corticotropes. Gel filtration of this beta-endorphin immunoreactivity indicates that approximately 3-fold more beta-endorphin than beta-lipotropin is released into plasma following these acute stressors. A similar preponderance of beta-endorphin over beta-lipotropin is seen in the media of short-term anterior lobe cell suspensions stimulated with ovine corticotropin-releasing hormone. Previous studies indicated that footshock stress, when administered repeatedly, can increase the biosynthesis of anterior lobe proopiomelanocortin (POMC) as indicated by increased steady state adrenocorticotropin/beta-endorphin content as well as increased POMC mRNA levels and increased POMC biosynthesis and rate of processing as measured by pulse-labeling and pulse-chase studies. The goal of the present studies was to determine whether this increased biosynthetic drive results in an alteration in the end products secreted with repeated stress. Acute footshock in a rat which has received 14 days of chronic footshock releases proportionately more beta-lipotropin than is released in a naive rat. Chronic electrically-induced seizures, which also increase anterior lobe POMC derived peptide stores, lead to a similar shift in the ratio of beta-lipotropin:beta-endorphin released following stress. These data suggest that chronic drive and the subsequent changes in POMC peptide stores may lead to a decrease in the proportion of beta-endorphin size immunoreactivity in the releasable pool of the anterior lobe corticotrope, thus altering the hormonal signal from the anterior lobe corticotrope.

Topics: Adrenocorticotropic Hormone; alpha-MSH; Animals; beta-Endorphin; beta-Lipotropin; Chromatography, Gel; Corticotropin-Releasing Hormone; Electroshock; Pituitary Gland, Anterior; Pro-Opiomelanocortin; Radioimmunoassay; Rats; Seizures; Stress, Psychological

The effects of the opiate antagonist, naloxone, on seizure tendencies of the black or nonagouti line of Mongolian gerbils (Meriones unguiculatus) carrying the a/a coat color allele was investigated. The animals were tested under the following conditions: mock infection; 0.9% NaCl injection; and naloxone at doses of 1, 2, 5, and 10 mg/kg body weight. The results indicated that when naloxone was at doses of 2 mg/kg body weight and higher, there was an increase in the animals' seizure latencies relative to that manifested under the basal condition.

Topics: Animals; beta-Endorphin; Brain; Dose-Response Relationship, Drug; Electroencephalography; Gerbillinae; Naloxone; Reaction Time; Seizures

Seizures, including electrically induced seizures (ECS), activate the hypothalamo-pituitary-adrenal (HPA) axis in rats. The present studies were undertaken to characterize the effects of repeated ECS on hormone release and brain adrenal steroid receptors. Repeated ECS led to an increase in adrenal weight, an increase in the corticosterone response to the eighth seizure compared to the first seizure, and an increase in basal plasma corticosterone levels at the trough of the circadian rhythm. Despite increased plasma corticosterone levels at the time of sacrifice, there were no decreases in adrenal steroid receptor numbers in hypothalamus, cortex or hippocampus. In chronic ECS-treated rats which were adrenalectomized overnight to remove glucocorticoids, an increase in Type I (mineralocorticoid) steroid receptors occurred in both hippocampus and cortex. These data suggest that chronic ECS has a trophic effect on Type I receptors and that the higher levels of corticosterone resulting from chronic ECS do not induce adrenal steroid receptor down-regulation.

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Brain Chemistry; Corticosterone; Electroshock; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Protein Binding; Radioimmunoassay; Rats; Rats, Inbred Strains; Receptors, Steroid; Seizures

Pentylenetetrazol (PTZ, 45 mg/kg, ip) impaired retention of a one-trial step-through inhibitory avoidance task when injected into male Swiss mice 10 min after training, as indicated by retention performance 48 h later. The amnestic effect of PTZ was prevented by naltrexone (0.01 or 0.10 mg/kg, ip) administered after training, but prior to PTZ-treatment. On the contrary, neither naltrexone methyl bromide (0.01, 0.10, or 10.0 mg/kg, ip), a quaternarium analog of naltrexone, nor MR2266 (0.01 or 0.10 mg/kg, ip), a putative kappa opiate receptor antagonist, modified the behavioral effects of PTZ. On the other hand, the body seizures produced by PTZ were unaffected by any of the three opiate receptor antagonists that were given before the convulsant. Taken together, these results suggest that the effects of PTZ on retention are mediated, at least in part, by opioid peptides of central origin, and rules out a possible participation of opioid peptides derived from prodynorphin-precursor molecule. Administration of beta-endorphin (0.01 or 0.10 microgram/kg, ip) 10 min prior to testing attenuate the retrograde amnesia caused by PTZ. The effect of beta-endorphin was prevented by the simultaneous administration of naltrexone (0.10 mg/kg, ip) prior to testing. Naltrexone has no effect of its own upon retrieval. These results suggest that the impairment of retention induced by PTZ is probably due, at least in part, to a release of opioid peptides in the brain during the post-training period. PTZ given after training do not affect consolidation or memory storage, as mice thus treated may retrieve the learned information when they are submitted to an appropriate neurohumoral and/or hormonal state in the test session, that is, beta-endorphin injection. Therefore, the action of PTZ would be primarily at the level of the mechanism that make stored information available for late retrieval.

Topics: Animals; Avoidance Learning; Benzomorphans; beta-Endorphin; Brain; Dose-Response Relationship, Drug; Male; Memory; Mice; Mice, Inbred Strains; Naltrexone; Narcotic Antagonists; Pentylenetetrazole; Quaternary Ammonium Compounds; Receptors, Opioid; Retention, Psychology; Seizures

Topics: Adrenocorticotropic Hormone; Animals; Baclofen; Behavior, Animal; beta-Endorphin; Brain; Diazepam; Endorphins; gamma-Aminobutyric Acid; In Vitro Techniques; Injections, Intraventricular; Naloxone; Pain; Pituitary Gland; Rats; Receptors, GABA-A; Receptors, Opioid; Seizures; Zinc

The effects of repeated infusion of small, initially subconvulsive amounts of beta-endorphin, met-enkephalin or morphine sulfate into the amygdala and hippocampus were investigated. beta-endorphin and met-enkephalin evoked epileptiform spiking when infused into the posterior amygdala or ventral hippocampus. Morphine evoked epileptiform spiking when infused into the anterior amygdala. Naloxone blocked or terminated the spiking. Repetition of the infusions led to the gradual development of bilateral generalized convulsions by beta-endorphin and met-enkephalin and to the development of tolerance to morphine. An unexpected observation was that handling, immobilization or conspecific threat potentiated the epileptiform effects of beta-endorphin and morphine in many cases. These results suggest that endogenous opiate mechanisms might play a role in convulsive seizures and that stressful stimuli can exacerbate opiate seizures.

Topics: Animals; beta-Endorphin; Brain; Electroencephalography; Endorphins; Enkephalin, Methionine; Handling, Psychological; Kindling, Neurologic; Male; Morphine; Naloxone; Rats; Seizures

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.

Topics: Animals; beta-Endorphin; Electroshock; Endorphins; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Male; Mice; Mice, Inbred C57BL; Morphine; Naltrexone; Narcotics; Seizures; Time Factors

Rats ranging in postnatal age from 6 hours to 28 days were implanted with cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. We then administered varying amounts of the opiate peptides leucine-enkephalin and beta-endorphin intracerebroventricularly with continuous electroencephalographic monitoring. Leucine-enkephalin produced electrical seizure activity in rats as young as 2 days. beta-Endorphin administration was associated with seizures at the fifth postnatal day, with a high incidence of apnea resulting in death in animals as young as 6 hours. An adult seizure response to beta-endorphin and leucine-enkephalin was seen at 15 and 28 days of age, respectively. Naloxone blocked the seizure produced by these opiate peptides in all age groups. The data indicate that the opiate peptides are potent epileptogenic compounds in developing brain, that seizures induced by leucine-enkephalin differ from those caused by beta-endorphin, and that petit mal-like seizure activity can be an adult response in the rodent.

Topics: Aging; Animals; beta-Endorphin; Brain; Electroencephalography; Endorphins; Enkephalin, Leucine; Evoked Potentials; Male; Naloxone; Rats; Rats, Inbred Strains; Seizures

A possible contribution of brain beta-endorphin and somatostatin to the epileptogenicity established by amygdaloid kindling was investigated in rats. Fourteen male rats were chronically implanted with electrodes placed bilaterally into the amygdala. The rats received 1 sec of electrical stimulation to the left amygdala each day. Generalized seizures were observed on average 10 days after initiation of kindling and the electrical stimulation was continued up to twenty-one days. Two months after the completion of the kindling procedure, each kindled and control rat was killed by microwave irradiation and the brains were dissected on ice into thirteen subregions. Each region was homogenized and centrifuged twice in 0.1 N acetic acid. The supernatant extracts were decanted and stored at - 20 degrees C until assay. Immunoreactive beta-endorphin and somatostatin were measured by radioimmunoassays. There were no significant differences in brain beta-endorphin contents between the two groups. In kindled rats, immunoreactive somatostatin was increased significantly in amygdala, sensorimotor, piriform, and entorhinal cortex. The results suggest that changes in somatostatin may be associated with epileptic susceptibility induced by the electrical kindling procedure.

Topics: Amygdala; Animals; beta-Endorphin; Brain; Electric Stimulation; Endorphins; Male; Rats; Seizures; Somatostatin; Tissue Distribution

The naturally epileptic Mongolian gerbil was used to investigate the epileptogenic properties of beta-endorphin, dynorphin, met-enkephalin and morphine. The results indicate that opioid induced "seizures" are different from naturally spontaneous seizures in the gerbil in respect to EEG recording and motor behavior. Evidence for a protective role in preventing seizures is also presented.

Topics: Animals; beta-Endorphin; Cerebral Cortex; Dynorphins; Endorphins; Enkephalin, Methionine; Epilepsy; Gerbillinae; Morphine; Naltrexone; Narcotics; Seizures

Resting pituitary levels of beta-endorphin-(beta-EP-IR), ACTH-(ACTH-IR), and alpha-MSH-(alpha-MSH-IR)-like immunoreactive material were found to differ among 16 inbred mouse strains. Hormone levels correlated genetically with severity of withdrawal from ethanol, which also differed among the strains. Ethanol dependence led to reduced pituitary beta-EP-IR in 4 of 5 strains studied. After 24 hr of withdrawal, 3 of those 4 showed elevated pituitary beta-EP-IR. These results are consistent with the hypothesis that genetically-determined difference in pituitary hormone functioning underlie some of the genetically-determined differences in ethanol withdrawal severity.

Topics: Adrenocorticotropic Hormone; Alcoholism; Animals; beta-Endorphin; Endorphins; Ethanol; Humans; Male; Melanocyte-Stimulating Hormones; Mice; Mice, Inbred Strains; Pituitary Gland; Seizures; Substance Withdrawal Syndrome

Topics: Animals; Behavior, Animal; beta-Endorphin; Electroshock; Endorphins; Mice; Pentylenetetrazole; Seizures

Topics: Animals; Anticonvulsants; beta-Endorphin; Dose-Response Relationship, Drug; Endorphins; Enkephalin, Methionine; Enkephalins; Etorphine; Flurothyl; Male; Morphinans; Naloxone; Rats; Rats, Inbred Strains; Seizures; Structure-Activity Relationship

Topics: Animals; beta-Endorphin; Brain; Brain Mapping; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Evoked Potentials; Interneurons; Kindling, Neurologic; Neural Inhibition; Neurons; Pituitary Gland; Rats; Receptors, Opioid; Seizures

Iontophoretic and micropressure drug application and lesion techniques were used to investigate the cellular source of rat limbic system epileptiform responses to opioid peptides [19]. Iontophoretically applied morphine, methionine enkephalin or beta-endorphin inhibited the spontaneous or glutamate-activated firing of the great majority of single neurons in medial and lateral septum, amygdala and cingulate cortex. These inhibitions in firing were antagonized by iontophoresis of naloxone. In contrast to inhibitory effects in other limbic areas, morphine and the opioid peptides predominantly excited CA1 and CA3 pyramidal neurons in a naloxone-sensitive manner, as previously reported [36]. On rare occasions, iontophoretically applied beta-endorphin evoked repetitive waveforms similar to interictal population EPSPs or spikes. Micropressure application of opiates and peptides also excited hippocampal neurons indicating such responses were not current-induced artefacts. The possible role of the excitatory cholinergic septal hippocampal pathway in the facilitatory response of hippocampal units to the opiates was tested with iontophoretically applied atropine and scopolamine, or lesions of septal nuclei. None of these manipulations reduced the opioid-induced excitations; rather, septal lesions enhanced excitatory and epileptiform responses to the opiates. These results support the hypothesis that opiate-evoked epileptiform activity in the limbic system arises from enhanced pyramidal cell activity in the hippocampal formation, probably by a non-cholinergic mechanism.

Topics: Action Potentials; Amygdala; Animals; beta-Endorphin; Endorphins; Enkephalin, Methionine; Enkephalins; Gyrus Cinguli; Hippocampus; Iontophoresis; Limbic System; Male; Morphine; Neurons; Pressure; Rats; Seizures; Septal Nuclei