Mu-delta opioid interactions. I: The delta peptide, DPDPE, increases morphine-induced EEG and EEG spectral power.

The effects of the selective delta peptide, DPDPE ([2-D-penicillamine,5-D-penicillamine]enkephalin), on morphine-induced EEG and EEG power spectra were assessed. Adult female Sprague-Dawley rats were implanted with cortical EEG electrodes and permanent indwelling ICV and IV cannulae. Rats were pretreated with ICV sterile water or ICV DPDPE at 1.25, 2.5, or 5.0 nmol, 10 min before receiving IV morphine at 3 mg/kg. The treatments produced high voltage EEG bursts and associated behavioral stupor. The EEG data were further analyzed on a Pathfinder II computer and statistical analysis of EEG spectral parameters was performed by using a one-way ANOVA followed by Turkey's HSD. ICV DPDPE at 2.5 nmol and 5.0 nmol significantly increased EEG absolute global spectral power. Furthermore, ICV DPDPE at 2.5 and 5.0 nmol significantly increased the duration of morphine-induced high voltage EEG bursts. These data further indicate an in vivo interaction between mu and delta opioid receptors.     

In vitro interactions of opioid peptides with phospholipids. II. Additional spectral evidence

The interaction of leu-enkephalin with phosphatidylserine has been studied with ultraviolet and circular dichroism spectroscopy methods as well as with fluorescence anisotropy techniques. The data reported hereunder confirm the existence of binding between the two species, and also support the hypothesis that not only the tyrosine, but also the phenylalanine residue in the leu-enkephalin molecule is involved in peptide-lipid interaction. In addition, ultraviolet and CD evidence, taken together, tend to suggest that both aromatic residues are bound, with a different degree of involvement, to the same region of the lipid molecule. The data reported are discussed in terms of the interaction model previously proposed by us.     

Antinociceptive interactions of opioid delta receptor agonists with morphine in mice: supra- and sub-additivity.

In this study, the antinociceptive interactions of fixed ratio combinations of intracerebroventricularly (i.c.v.) given morphine and subantinociceptive doses of the delta agonists, [D-Pen2, D-Pen5]enkephalin (DPDPE), [D-Ala2, Glu4]deltorphin (DELT) or [Met5]enkephalin (MET) were examined using the mouse warm water tail flick test. When morphine was coadministered with DPDPE or DELT in a 4:1 and 9:1 mixture, respectively, a synergistic antinociceptive effect was observed. In contrast, when morphine was coadministered with MET in a 1:2 fixed ratio mixture, a subadditive interaction occurred. These results demonstrate both positive and negative modulatory interactions of delta agonists with morphine in an antinociceptive endpoint and that these interactions can be either supra- or subadditive. The data support the concept of a functional interaction between opioid mu and delta receptors and a potential regulatory role for the endogenous ligands of the opioid delta receptor.     

II - Prostaglandin hyperalgesia: the peripheral analgesic activity of morphine, enkephalins and opioid antagonists.

Morphine, enkephalins, nalorphine, naloxone and pentazocine are shown to have a peripheral analgesic effect. In our modification of the Randall-Selitto test these substances were 50--100 times more potent than a standard local anaesthetic, lidocaine. At this peripheral site, naloxone did not antagonize the effect of morphine. Morphine had a marked analgesic effect on the hyperalgesia induced by PGE2 and PGI2, BaCl2, Ca2+ ionophore A23187, isoprenaline but not on that induced by dibutyryl cyclic AMP. It was suggested that the peripheral analgesic effect of morphine is due to an inhibition of adenylate-cyclase activity.     

EEG power spectral density in locked-in and completely locked-in state patients: a longitudinal study

Persons with their eye closed and without any means of communication is said to be in a completely locked-in state (CLIS) while when they could still open their eyes actively or passively and have some means of communication are said to be in locked-in state (LIS). Two patients in CLIS without any means of communication, and one patient in the transition from LIS to CLIS with means of communication, who have Amyotrophic Lateral Sclerosis were followed at a regular interval for more than 1 year. During each visit, resting-state EEG was recorded before the brain–computer interface (BCI) based communication sessions. The resting-state EEG of the patients was analyzed to elucidate the evolution of their EEG spectrum over time with the disease’s progression to provide future BCI-research with the relevant information to classify changes in EEG evolution. Comparison of power spectral density (PSD) of these patients revealed a significant difference in the PSD’s of patients in CLIS without any means of communication and the patient in the transition from LIS to CLIS with means of communication. The EEG of patients without any means of communication is devoid of alpha, beta, and higher frequencies than the patient in transition who still had means of communication. The results show that the change in the EEG frequency spectrum may serve as an indicator of the communication ability of such patients.Electronic supplementary materialThe online version of this article (10.1007/s11571-020-09639-w) contains supplementary material, which is available to authorized users.     

The relationship between short-term memory capacity and EEG power spectral density

Multiplying memory span by mental speed, we obtain the information entropy of short-term memory capacity, which is rate-limiting for cognitive functions and corresponds with EEG power spectral density. The number of EEG harmonics (n = 1, 2,, 9) is identical with memory span, and the eigenvalues of the EEG impulse response are represented by the zero-crossings up to the convolved fundamental, the P300. In analogy to quantum mechanics the brain seems to be an ideal detector simply measuring the energy of wave forms. No matter what the stimulus is and how the brain behaves, the metric of signal and memory can always be understood as a superposition of n states of different energy and their eigenvalues.     

功率谱熵在痫性发作大鼠脑电检测中的应用研究

目的:研究功率谱熵在痫性发作大鼠脑电检测中的应用。方法:采用青霉素在大鼠海马微注射制备急性痫性发作模型,以深部电极记录大鼠原始脑电信号,将24只SD大鼠随机分成四组,即正常组(A),对照组(B),单电极组(C),多电极组(D)。C、D组大鼠经致痫后观察未发作期、发作前期、发作期和发作后期四期脑电信号的变化,运用谱熵对四期脑电信号进行分析,并与A、B组进行对比。结果:C组和D组脑电功率谱熵显示两组发作期与未发作期、发作前期、发作后期比较有显著差异(P0.05),发作期明显低于其它各期;未发作期和发作前期相比有明显差异(P0.05),发作前期较未发作期降低;将D组大鼠海马致痫灶(a)及其同侧附近(b)、对侧(c)三点发作各期脑电功率谱熵进行对比分析,发作前期和发作期a、b、c三点比较有明显差异(P0.05),a点最低,c点的功率谱熵值最高。结论:功率谱熵可以预报痫性发作并可对癫痫病灶的定位提供一定的帮助。     

Relations between anxiolytic effects of diazepam and changes in the EEG spectral power

The influence of diazepam (1; 5; 10 mg/kg, i. p.), chlorpromazine (1 mg/kg) and amphetamine (1; 5 mg/kg) on the Fourier's spectral EEG power of sensomotor cortex and dorsal hippocampus and conflict behavior freely moving albino and cotton (Sigmondon hispidus) rats was studied. Effects of diazepam (5 mg/kg) in cotton rats were similar, but influence on the theta-activity was more expressed. Correlation between slowing of theta-activity and extent of anxiolytic effect in conflict situation was showed. On the basis of the results obtained the authors discuss possible mutual relations between the influence of diazepam on EEG and anxiolytic effect of benzodiazepines.     

II - Prostaglandin hyperalgesia: The peripheral analgesic activity of morphine, enkephalins and opioid antagonists

Morphine, enkephalins, nalorphine, naloxone and pentazocine are shown to have a peripheral analgesic effect. In our modification of the Randall-Selitto test these substances were 50–100 times more potent than a standard local anaesthetic, lidocaine. At this peripheral site, naloxone did not antagonize the effect of morphine. Morphine had a marked analgesic effect on the hyperalgesia induced by PGE₂ and PGI₂, BaCl₂, Ca²⁺ ionophore A23187, isoprenaline but not on that induced by dibutyryl cyclic AMP. It was suggested that the peripheral analgesic effect of morphine is due to an inhibition of adenylate-cyclase activity.     

Adenosine deaminase polymorphism affects sleep EEG spectral power in a large epidemiological sample

Slow wave oscillations in the electroencephalogram (EEG) during sleep may reflect both sleep need and intensity, which are implied in homeostatic regulation. Adenosine is strongly implicated in sleep homeostasis, and a single nucleotide polymorphism in the adenosine deaminase gene (ADA G22A) has been associated with deeper and more efficient sleep. The present study verified the association between the ADA G22A polymorphism and changes in sleep EEG spectral power (from C3-A2, C4-A1, O1-A2, and O2-A1 derivations) in the Epidemiologic Sleep Study (EPISONO) sample from São Paulo, Brazil. Eight-hundred individuals were subjected to full-night polysomnography and ADA G22A genotyping. Spectral analysis of the EEG was carried out in all individuals using fast Fourier transformation of the signals from each EEG electrode. The genotype groups were compared in the whole sample and in a subsample of 120 individuals matched according to ADA genotype for age, gender, body mass index, caffeine intake status, presence of sleep disturbance, and sleep-disturbing medication. When compared with homozygous GG genotype carriers, A allele carriers showed higher delta spectral power in Stage 1 and Stages 3+4 of sleep, and increased theta spectral power in Stages 1, 2 and REM sleep. These changes were seen both in the whole sample and in the matched subset. The higher EEG spectral power indicates that the sleep of individuals carrying the A allele may be more intense. Therefore, this polymorphism may be an important source of variation in sleep homeostasis in humans, through modulation of specific components of the sleep EEG.     

EEG correlates of hypnotic susceptibility based upon fast Fourier power spectral analysis

The purpose of the present study was to determine if there were differences between high and low hypnotic susceptible subjects based upon fast Fourier power spectral analysis of the EEG recorded both before and during hypnotic tasks from frontal-temporal and occipital-parietal locations. Significant differences were obtained based upon EEG recording electrode location, EEG frequency within six different frequency domains, and hypnotic tasks. However, no main effect differences were obtained based upon hypnotic susceptibility. In contrast to some evoked potential studies in which a few differences have been obtained based on hypnotic susceptibility the lack of any EEG differences in this study even when positive and negative hallucination tasks were employed may have implications for the role of the neocortex in mediating hypnotic phenomena.     

Relation of endogenous opioid peptides and morphine to neuroendocrine functions.

Morphine and the endogenous opioid peptides (EOP) exert similar effects on the neuroendocrine system. When adminstered acutely, they stimulate growth hormone (GH), prolactin (PRL), and adrenocorticotropin (ACTH) release, and inhibit release of luteinizing hormone (LH), follicle stimulating hormone (FSH),and thyrotropin (TSH). Recent studies indicate that the EOP probably have a physiological role in regulating pituitary hormone secretion. Thus injection of naloxone (opiate antagonist) alone in rats resulted in a rapid fall in serum concentrations of GH and PRL, and a rise in serum LH and FSH, suggesting that the EOP help maintain basal secretion of these hormones. Prior administration of naloxone or naltrexon inhibited stress-induced PRL release, and elevated serum LH in castrated male rats to greater than normal castrate levels. Studies on the mechanisms of action of the EOP and morphine on hormone secretion indicate that they have no direct effect on the pituitary, but act via the hypothalamus. There is no evidence that the EOP or morphine alter the action of the hypothalamic hypophysiotropic hormones on pituitary hormone secretion; they probably act via hypothalamic neurotransmitters to influence release of the hypothalamic hormones into the pituitary portal vessels. Preliminary observations indicate that they may increase serotonin and decrease dopamine metabolism in the hypothalamus, which could account for practically all of their effects on pituitary hormone secretion.     

Phosphorylation of PS II polypeptides inhibits D1 protein-degradation and increases PS II stability

To study the significance of Photosystem (PS) II phosphorylation for the turnover of the D1 protein, phosphorylation was compared with the synthesis and content of the D1 protein in intact chloroplasts. As shown by radioactive labelling with [³²P_i] phosphorylation of PS II polypeptides was saturated at light intensities of 125 mol m^-2 s^-1. Under steady state conditions, in intact chloroplasts D1 protein, once it was phosphorylated, was neither dephosphorylated nor degraded in the light. D1 protein-synthesis was measured as incorporation of [¹⁴C] leucine. As shown by non-denaturing gel-electrophoresis followed by SDS-PAGE newly synthesised D1 protein was assembled to intact PS II-centres and no free D1 protein could be detected. D1 protein-synthesis was saturated at light intensities of 500 mol m^-2 s^-1. The content of D1 protein stayed stable even after illumination with 5000 mol m^-2 s^-1 showing that D1 protein-degradation was saturated at the same light intensities. The difference in the light saturation points of phosphorylation and of D1 protein-turnover indicates a complex regulation of D1 protein-turnover by phosphorylation. Separation of the phosphorylated and dephosphorylated D1 protein by LiDS-gelelectrophoresis combined with radioactive pulse-labelling with [¹⁴C] leucine and [³²P_i] revealed that D1 protein, synthesised under steady state conditions in the light, did not become phosphorylated but instead was rapidly degraded whereas the phosphorylated form of the D1 protein was not a good substrate for degradation. According to these observations phosphorylation of the D1 protein creates a pool of PS II centres which is not involved in D1 to these observations phosphorylation of the D1 protein creates a pool of PS II centres which is not involved in D1 protein-turnover. Fractionation of thylakoid membranes confirms that the phosphorylated, non-turning over pool of PS II-centres was located in the central regions of the grana, whereas PS II-centres involved in D1 protein-turnover were found exclusively in the stroma-lamellae and in the grana-margins.Abbreviations chl chlorophyll - F_v yield of variable fluorescence, difference between F_m, the maximal fluorescence yield at saturating light, when all reaction-centres are closed, and F_o, the fluorescence yield in the dark, when all reaction-centres are open - LHC light harvesting complex - PFD photon flux density - PS photosystem     

Interhemispheric differences in the spectral power and coherence of EEG rhythms in children with autism spectrum disorders

Electroencephalographic examination of boys aged 4–9 years with autism spectrum disorders (ASDs) showed spectral power values and coherence in high-frequency bands (20–60 Hz) in various brain areas were higher than normal. Differences in spectral power were greater in the anterior areas of the left hemisphere; differences in coherence, in the right anterior and posterior areas. Interhemispheric differences typical of healthy subjects were absent in the children with ASDs. The spectral power of the θ rhythm was lower in autism, especially in the left hemisphere. The spectral power of the α rhythm in the autistic children was lower than normal, especially in the posterior areas of the left hemisphere. The μ rhythm was higher than normal in spectral power and was localized in the right, rather than left, anterior areas. The children were examined again after corrective procedures. The α-rhythm spectral power increased (became closer to the norm) in the left posterior areas, while the γ-rhythm spectral power decreased (became closer to the norm) in the right anterior areas in some of the autistic children. The electrophysiological changes were associated with improved psychological testing results, especially in nonverbal measures.     

Lung opioid receptors: pharmacology and possible target for nebulized morphine in dyspnea

Opioid receptors are located throughout the respiratory tract. Yet, these have received relatively scant attention compared to other opioid receptors. The most abundant sites within the respiratory tract appear localized within the alveolar walls, other sites appear to line the smooth muscle within the trachea and main bronchi near the lumen. There is about 100-times greater [3H]morphine binding density within the bronchioles and lobes than in the main bronchi or trachea. In addition to the usual mu, delta and kappa types of opioid receptors, 'non-conventional' opioid binding sites have been suggested, although the function of these or of the other opioid receptors in the pulmonary tract is not known. However, they might explain the otherwise counterintuitive apparent utility of morphine treatment of dyspnea. Dyspnea is a common and distressing symptom in terminally-ill cancer patients and patients with chronic lung disease. It results from multiple causes, is difficult to treat and is a significant precipitating factor for late-stage hospital or hospice admissions. Nebulized morphine or other opioids have been reported to have beneficial effect, but the mechanism by which opioids might produce this seemingly contradictory effect is not clear. We review here lung opioid receptor distribution, pharmacology and possible clinical relevance in the treatment of dyspnea.     

The spectral dynamics and its applications in EEG

The method of spectral dynamics is introduced to process slow changes in EEG. This method is based on evaluation of distance between EEG spectra. The typical application field is pharmaco-EEG after single dose drug administration, where distances between pre and post drug EEG spectra are computed. The distance between two spectra may be, however, defined in several different ways. The paper deals with the well known L _p metrics and with the metrics that plays an important role in discriminating stationary processes with different spectra. The L _p and metrics are non-equivalent and their properties, consistency and robustness, are studied in a simple statistical model.     

Interactions between purine derivatives: Electronic spectral studies. II. Excition interactions in the dimer of 6-methylpurine in aqueous solution

From a study of the concentration dependence of the ultraviolet absorption spectra of aqueous solutions of 6-methylpurine, the spectra of monomeric and dimeric species have been derived. The dichroic spectrum of 6-methylpurine in stretched poly(vinyl alcohol) films has been determined. The absorption envelope of 6-methylpurine up to 44,000 cm^?1 appears to include a low-intensity nitrogen (π*,n) transition at the low wavenumber tail and two additional electronic transitions of dominant intensities. Both the experimental dichroic ratios and theoretical calculations suggest that the letter two transitions are in-plane (π*,π) types. Analysis of the dimer species spectrum in terms of exciton interactions between molecules in “sandwich” conformation has been carried out. The interaction between the moments of the lowest energy (π*,π) transitions of the molecule in the dimer seems to result in transfer rates of energy of the order of 10¹³ sec^?1 between the two molecules.     

3-Carboxamido analogues of morphine and naltrexone. synthesis and opioid receptor binding properties.

In response to the unexpectedly high affinity for opioid receptors observed in a novel series of cyclazocine analogues where the prototypic 8-OH was replaced by a carboxamido group, we have prepared the corresponding 3-CONH(2) analogues of morphine and naltrexone. High affinity (K(i)=34 and 1.7nM) for mu opioid receptors was seen, however, the new targets were 39- and 11-fold less potent than morphine and naltrexone, respectively.