Delayed neuronal death in the gerbil hippocampus following ischemia

The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson9s and Huntington9s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB 1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB 1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB 2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients9 need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

http://www.phytecs.com/wp-content/uploads/2015/02/Pharmacol-Rev-2006-Pacher-389-462.pdf

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

/pdf/degradable-controlled-release-polymers-and-polymeric-1y322ha58z.pdf

Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release

http://www.diabetichealthclinic.org/wp-content/uploads/2014/04/nihms36189.pdf

Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake

Histamine is a transmitter in the nervous system and a signaling molecule in the gut, the skin, and the immune system. Histaminergic neurons in mammalian brain are located exclusively in the tuberomamillary nucleus of the posterior hypothalamus and send their axons all over the central nervous system. Active solely during waking, they maintain wakefulness and attention. Three of the four known histamine receptors and binding to glutamate NMDA receptors serve multiple functions in the brain, particularly control of excitability and plasticity. H1 and H2 receptor-mediated actions are mostly excitatory; H3 receptors act as inhibitory auto- and heteroreceptors. Mutual interactions with other transmitter systems form a network that links basic homeostatic and higher brain functions, including sleep-wake regulation, circadian and feeding rhythms, immunity, learning, and memory in health and disease.

Histamine in the Nervous System

To examine the possible relationship between the occurrence of menopausal hot flushes and waking episodes, a study was conducted of nine postmenopausal women with severe hot flushes and five asymptomatic premenopausal women. Measurement of simultaneous changes of finger temperature and skin resistance over the sternum was used as an objective marker of hot flushes. During cumulative sleep 47 objectively measured hot flushes occurred, and 45 were associated with a waking episode measured by polygraphic techniques. In eight of nine subjects, a significant correlation was observed between the occurrence of hot flushes and waking episodes. A similar association was not observed in premenopausal subjects. Estrogen administered to symptomatic patients resulted in significant reductions of both hot flushes and waking episodes. These data suggest that menopausal flushes are associated with a chronic sleep disturbance, and both can be improved by estrogen therapy. (JAMA1981;245:1741-1744)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=jama&articleId=374823&pdfFileName=jama_245_17_025.pdf

Association of Waking Episodes With Menopausal Hot Flushes

Summary

A new strain of selectively bred seizure-sensitive Mongolian gerbils is described. These WJL/UC gerbils exhibit stereotyped seizures in response to increased stimulus input that can be rated on a seven-point scale of severity. Integrated motor activity during seizures and latency and duration of seizures are related to severity. Susceptibility to seizures starts at 9 weeks and reaches 97% at 6 months. The severity increases from a mean of 1.2 at 2 months to 4.1 at 6 months of age. Death in seizure is rare. These attributes make the WJL/UC seizure-sensitive Mongolian gerbil suitable for testing as an animal model valid for study of the epilepsies.



Resume

On decrit une nouvelle lignee de gerbilles mongoliennes selectionnees qui presentent des crises epileptiques. Ces WJL/UC gerbilles presentent des crises stereotypies, dont L'intensite peut etre elassee suivant L'echelle de 0 a 7 points, lors d'un augmentation des stimulations afferentielles. L'activite motrice globale pendant les crises ainsi que la latence et la duree des crises sont en relation avec leur intensityes. La susceptibilitye aux crises apparait a 9 semaines et atteint les 97%a 6 mois. La severite augmente d'une moyenne de 1.2 a 2 mois a 4.1 a 6 mois d'âge. La mort pendant la crise est rare. Ces proprietes font de la gerbille mongolienne WJL/UC susceptible de faire des crises, un model souhaitable et valable dans 1'etude des epilepsies.



Zusammenfassung



Ein neuer Stamm selektiv anfallsempfindlicher mongoloider Gerbils* wird beschrieben. Diese WJL/UC Gerbils zeigen als Antwort auf vermehrte Reize stereotype Krampfe, deren Schwere nach einer 7-Punkte Skala bestimmt werden kann. Die integrierte motorische Aktivitat wahrend der Krampfe, ihre Latenz und Dauer sind abhangig von der Schwere der Krampfe. Die Fahigkeit zu krampfen beginnt mit 9 Wochen und ist mit 6 Monaten bei 97% det Tiere ausgepragt. Der Schweregrad der Anfalie steigt im Durchschnitt von 1.2 im Alter von 2 Monaten auf 4.1 im Alter von 6 Monaten. Ein Exitus wahrend der Anfalie ist selten. Diese Eigenschaften machen das WJL/UC anfallsempfindiche mongoloide Gerbil zu einem geeigneten Testobjekt fur das Studium der Epilepsien.



RESUMEN

Se describe una nueva raza de gerbiles mongolicos (roedor) selectivamente cultivados para hacerlos mas sensibles a ataques convulsivos. Estos WJL/UC roedores presentan ataques estereotipados ante estimulos que pueden clasificarse en una escala de siete puntos segun la severidad del ataque. La actividad motora integrada durante los episodios convulsivos asi como la latencia y'duracion de los ataques estan relacionados con su severidad. La susceptibilidad para dichos ataques comienza a las nuevo semanas y alcanza un 97% a los 6 meses. La severidad de las convulsiones aumenta de un promedio de 1.2 a los 2 meses a 4.1 a los 6 meses de edad. La muerte en pleno ataque es rara. Todas estas characteristicas hacen que el gerbil monogolico WJL/UC, sensible a las convulsiones sea adecuado como animal testigo para el estudio de las epilepsias.

The gerbil as a model for the study of the epilepsies. Seizure patterns and ontogenesis.

A stereotaxic atlas of the Mongolian gerbil brain (Meriones unguiculatus)

Morphine hyperthermia in the rat: An action of the central thermostats

The effect of morphine sulfate on the body temperature of the rat has been investigated. With a dose of 10 mg/kg administered intravenously there occurred a marked fall in core temperature and the degree and duration of hypothermia increased to give a maximum response with 35-50 mg/kg. Doses of 1 and 5 mg/kg caused either no change or a rise in temperature. Injection of 50 µg morphine sulfate into the region of the preoptic/anterior hypothalamic nuclei also led to a fall in core temperature, while injections into other regions of the hypothalamus were ineffective. Introduction of the drug into the area of the mammillary nuclei caused hyperactivity and hyperthermia. It is suggested that the hypothermic effect of morphine is due to depression of the set point of the thermoregulatory center in the anterior hypothalamus.

Peter Lomax

Papers

Association of Waking Episodes With Menopausal Hot Flushes

The gerbil as a model for the study of the epilepsies. Seizure patterns and ontogenesis.

A stereotaxic atlas of the Mongolian gerbil brain (Meriones unguiculatus)

Morphine hyperthermia in the rat: An action of the central thermostats

Temperature responses in the rat following intracerebral microinjection of morphine