Diazepam, Pentobarbital, And Methaqualone Effects On Several Behaviors In The Rat And Antagonism By Ro 15-1788

The sedative hypnotics may exert their effects through a number of different mechanisms. Diazepam interacts with a specific receptor linked to a GABA receptor and a CL ionophore (Skolnick and Paul, 1981) and enhances the binding affinity of the GABA receptor for its ligand. Barbiturates may act at an additional receptor linked to this complex (Olsen, 1981). The sites of action of methaqualone have yet to be defined. Recently Hunkeler et al. (1981) synthesized a new class of compounds, the imidazodiazepines, the prototype being Ro 15-1788. They showed that Ro 15-1788 inhibits 3H-Diazepam binding to brain synaptosomes, reverses diazepam-induced protection against metrazol seizures, and alleviates the disruption induced by diazepam in a horizontal wire test. Ro 15-1788 does not affect the depression induced by Phenobarbital, meprobamate or ethanol. In a standard conflict paradigm Ro 15-1788 prevents the antipunishment effect of diazepam. Ro 15-1788 also antagonizes the decrease in rat cerebellar cGMP by diazepam, but not that by barbiturates, ethanol or meprobamate (Mohler et al., 1981), and reverses the effects of 3-methylclonazepam in a number of tests in humans (Darragh et al., 1981). We have investigated the effects of diazepam (DZ), pentobarbital (PB) and methaqualone (MQ) alone and in combination with Ro 15-1788 in a novel conflict paradigm, conditioned suppression of drinking (CSD), as well as in rotarod performance (RR) and motor activity (MA)

Effects of Combined Opioids on Pain and Mood in Mammals

The authors review the opioid literature for evidence of increased analgesia and reduced adverse side effects by combining mu-opioid-receptor (MOR) agonists, kappa-opioid-receptor (KOR) agonists, and nonselective low-dose-opioid antagonists (LD-Ant). We tested fentanyl (MOR agonist) and spiradoline (KOR agonist), singly and combined, against somatic and visceral pain models. Combined agonists induced additive analgesia in somatic pain and synergistic analgesia in visceral pain. Other investigators report similar effects and reduced tolerance and dependence with combined MOR agonist and KOR agonist. LD-Ant added to either a MOR agonist or KOR agonist markedly enhanced analgesia of either agonist. In accordance with other place-conditioning (PC) studies, our PC investigations showed fentanyl-induced place preference (CPP) and spiradoline-induced place aversion (CPA). We reduced fentanyl CPP with a low dose of spiradoline and reduced spiradoline CPA with a low dose of fentanyl. We propose combined MOR agonist, KOR agonist, and LD-Ant to produce superior analgesia with reduced adverse side effects, particularly for visceral pain

Fentanyl And Spiradoline Interactions In A Place-Conditioning Black-White Shuttle-Box

Rats were trained for multiple sessions in a place-conditioning shuttle-box to explore motivational interactions of mu and kappa opioid agonists, specifically fentanyl reward and spiradoline aversion. In Phase 1, groups of rats received various doses of mu or kappa agonists, or placebo, testing for preference or aversion. Group A always received saline SC before 15-minute sessions. Group B received fentanyl SC (0.003, 0.006, 0.012 mg/kg), Group C received low and medium doses of agonists SC, and Group D received spiradoline (0.3, 0.6, 1.2 mg/kg) SC during Training Sessions 1-4, rats being restricted to the drug-associated compartment. Rats received saline when restricted to the placebo-associate compartment and on test days with access to both shuttle-box compartments. In Phase 2 of the study, Training Session 5, Combinations of mu and kappa agonists were substituted in Groups B, C, and D. Dose-related preference to fentanyl and aversion to spiradoline occurred during Test Sessions 1-4. During Test Session 5, fentanyl preference in Group B was suppressed by spiradoline, rats in Group C had a saline-like response to combined agonists, and spiradoline aversion in Group D was attenuated by fentanyl. These findings suggest that combined doses of mu and kappa agonists, while additive for antinociception, offset the rewarding and punishing effects of each other

Behavioral Interactions Of Opioid Agonists And Antagonists With Serotonergic Systems

Morphine interacts with brain serotonergic (5-HT) systems; these systems have been implicated in morphine analgesia and dependence (see Cervo et al., 1981). The 5-HT agonist quipazine induces analgesia in rats that is attenuated by naloxone and 5-HT antagonists (Minnema et al., 1980; Samanin et al., 1976). Behavioral disruption by the hallucinogens LSD, DMT and mescaline, mediated primarily through brain 5-HT effects (Rech and Commissaris, 1982), is potentiated by naloxone and naltrexone (Commissaris et al., 1980; Ruffing and Domino, 1981) and is variably antagonized or potentiated by morphine and methadone (Ruffing and Domino, 1981). Cyclazocine causes a disruption of operant behavior similar to that of the hallucinogens which is reversed in part by nalozone and the 5-HT antagonist metergoline, and to a greater extent by the combination of maloxone and metergoline (Henck et al., 1983). These studies indicate that indole and phenethylamine hallucinogens interact to some extent with brain opioid mechanisms as well as brain 5-HT components, whereas opioid drugs influence behavior in part by actions on 5-HT systems. We have extended these drug studies in an attempt to characterize interactions with 5-HT mechanisms and to identify the various types of opioid receptors involved

GHz QKD at telecom wavelengths using up-conversion detectors

We have developed a hybrid single photon detection scheme for telecom wavelengths based on nonlinear sum-frequency generation and silicon single-photon avalanche diodes (SPADs). The SPAD devices employed have been designed to have very narrow temporal response, i.e. low jitter, which we can exploit for increasing the allowable bit rate for quantum key distribution. The wavelength conversion is obtained using periodically poled Lithium niobate waveguides (W/Gs). The inherently high efficiency of these W/Gs allows us to use a continuous wave laser to seed the nonlinear conversion so as to have a continuous detection scheme. We also present a 1.27GHz qubit repetition rate, one-way phase encoding, quantum key distribution experiment operating at telecom wavelengths that takes advantage of this detection scheme. The proof of principle experiment shows a system capable of MHz raw count rates with a QBER less than 2% and estimated secure key rates greater than 100 kbit/s over 25 km.Comment: 12 pages, 7 figure

Conductance of Tomonaga-Luttinger liquid wires and junctions with resistances

We study the effect that resistive regions have on the conductance of a quantum wire with interacting electrons which is connected to Fermi liquid leads. Using the bosonization formalism and a Rayleigh dissipation function to model the power dissipation, we use both scattering theory and Green's function techniques to derive the DC conductance. The resistive regions are generally found to lead to incoherent transport. For a single wire, we find that the resistance adds in series to the contact resistance of h/e^2 for spinless electrons, and the total resistance is independent of the Luttinger parameter K_W of the wire. We numerically solve the bosonic equations to illustrate what happens when a charge density pulse is incident on the wire; the results depend on the parameters of the resistive and interacting regions in interesting ways. For a junction of Tomonaga-Luttinger liquid wires, we use a dissipationless current splitting matrix to model the junction. For a junction of three wires connected to Fermi liquid leads, there are two families of such matrices; we find that the conductance matrix generally depends on K_W for one family but is independent of K_W for the other family, regardless of the resistances present in the system.Comment: 6 pages, 3 figures; added a discussion of time reversal invariance; this is the published versio

Serum neuron-specific enolase as early predictor of outcome after in-hospital cardiac arrest: a cohort study

INTRODUCTION: Outcome after cardiac arrest is mostly determined by the degree of hypoxic brain damage. Patients recovering from cardiopulmonary resuscitation are at great risk of subsequent death or severe neurological damage, including persistent vegetative state. The early definition of prognosis for these patients has ethical and economic implications. The main purpose of this study was to investigate the prognostic value of serum neuron-specific enolase (NSE) in predicting outcomes in patients early after in-hospital cardiac arrest. METHODS: Forty-five patients resuscitated from in-hospital cardiac arrest were prospectively studied from June 2003 to January 2005. Blood samples were collected, at any time between 12 and 36 hours after the arrest, for NSE measurement. Outcome was evaluated 6 months later with the Glasgow outcome scale (GOS). Patients were divided into two groups: group 1 (unfavorable outcome) included GOS 1 and 2 patients; group 2 (favorable outcome) included GOS 3, 4 and 5 patients. The Mann–Whitney U test, Student's t test and Fisher's exact test were used to compare the groups. RESULTS: The Glasgow coma scale scores were 6.1 ± 3 in group 1 and 12.1 ± 3 in group 2 (means ± SD; p < 0.001). The mean time to NSE sampling was 20.2 ± 8.3 hours in group 1 and 28.4 ± 8.7 hours in group 2 (p = 0.013). Two patients were excluded from the analysis because of sample hemolysis. At 6 months, favorable outcome was observed in nine patients (19.6%). Thirty patients (69.8%) died and four (9.3%) remained in a persistent vegetative state. The 34 patients (81.4%) in group 1 had significantly higher NSE levels (median 44.24 ng/ml, range 8.1 to 370) than those in group 2 (25.26 ng/ml, range 9.28 to 55.41; p = 0.034). CONCLUSION: Early determination of serum NSE levels is a valuable ancillary method for assessing outcome after in-hospital cardiac arrest

Effects of various drugs on activity of the neuronally isolated cerebral cortex

The topical application of strychnine, d-tubocurarine, pentylenetetrazole, picrotoxin, and physostigmine evoked different patterns of electrical activity in a portion of the acutely isolated suprasylvian gyrus of dogs. Pentylenetetrazole and picrotoxin evoked a similar pattern of activity in the isolated gyrus by both topical application and intravenous administration. Reasonable systemic doses of strychnine, d-tubocurarine and physostigmine did not produce activity similar to that seen on topical application. Therefore, the effects obtained by topical application of drugs to the cerebral cortex must be interpreted cautiously as regarding the usual pharmacological actions of these agents. Adrenergic agents, administered systemically, exerted a diphasic effect upon chemically and electrically evoked activity. An initial depression and subsequent enhancement were observed. These actions were exceedingly variable and did not appear to be secondary to vascular effects. On the other hand the effects of acetylcholine and arecoline did seem to be secondary to their cardiovascular effects. Since entirely different patterns of spontaneous and evoked electrical activity could be recorded simultaneously from the isolated and nearby intact portions of the cortex, it was concluded that the neuronally isolated cerebral cortex gave rise to independent activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32408/1/0000485.pd

Characterization of a new genotype of avian bornavirus from wild ducks

BACKGROUND: Avian bornaviruses (ABV) are a recently described group of intranuclear negative-stranded RNA viruses (Order Mononegavirales, Family Bornaviridae). At least 13 different ABV genotypes have been described. One genotype, the Canada goose genotype (ABV-CG), has been isolated from geese and swans and is widely distributed across North America. RESULTS: We have isolated and characterized a previously undescribed genotype of avian bornavirus from the brains of wild ducks. This new genotype, provisionally designated ABV genotype MALL, was detected in 12 of 83 mallards, and 1 of 8 wood ducks collected at a single location in central Oklahoma. The virus was cultured on primary duck embryo fibroblasts, fragments were cloned, and its genome sequence of 8904 nucleotides determined. This new genotype has 72% nucleotide identity and 83% amino acid identity with the ABV-CG genotype previously shown to be present in geese and swans. Histologic and immunohistochemical examination of the brains and eyes of four positive ducks indicated the presence of virus-infected neurons and glia in their cerebrums and retinas in the absence of inflammation. CONCLUSIONS: More than one genotype of ABV is circulating in North American waterfowl. While the infected ducks were not observed to be suffering from overt disease, based on the immunohistochemistry, we speculate that they may have suffered some visual impairment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-014-0197-9) contains supplementary material, which is available to authorized users