Elaine Elisabetsky

Effects of Linalool on Glutamatergic System in the Rat Cerebral Cortex

Linalool is a monoterpene compound reported to be a major component of essential oils in, various aromatic species. Several Linalool-producing species are used in traditional medical systems, includingAeolanthus suaveolens G. Dom (Labiatae) used as anticonvulsant in the Brazilian Amazon. Psychopharmacological in vivo evaluation of Linalool showed that this compound have dose-dependent marked sedative effects at the Central Nervous System, including hypnotic, anticonvulsant and hypothermic properties. The present study reports an inhibitory effect of Linalool on Glutamate binding in rat cortex. It is suggested that this neurochemical effect might be underlining Linalool psychopharmacological effects. These findings provide a rational basis for many of the traditional medical use of Linalool producing plant species.

Anticonvulsant properties of linalool in glutamate-related seizure models.

In order to investigate the pharmacodynamic basis of the previously-established anticonvulsant properties of linalool, we examined the effects of this compound on behavioral and neurochemical aspects of glutamate expression in experimental seizure models. Specifically, linalool effects were investigated to determine its inhibition of (i) L-[3H]glutamate binding at CNS (central nervous system membranes), (ii) N-methyl-D-aspartate (NMDA)-induced convulsions, (iii) quinolinic acid (QUIN)-induced convulsions, and the behavioral and neurochemical correlates of PTZ-kindling. The data indicate that linalool modulates glutamate activation expression in vitro (competitive antagonism of L-[3H]glutamate binding) and in vivo (delayed NMDA convulsions and blockage of QUIN convulsions). Linalool partially inhibited and significantly delayed the behavioral expression of PTZ-kindling, but did not modify the PTZ-kindling-induced increase in L-[3H]glutamate binding.

Inhaled linalool-induced sedation in mice.

Linalool is a monoterpene often found as a major component of essential oils obtained from aromatic plant species, many of which are used in traditional medical systems as hypno-sedatives. Psychopharmacological evaluations of linalool (i.p. and i.c.v.) revealed marked sedative and anticonvulsant central effects in various mouse models. Considering this profile and alleged effects of inhaled lavender essential oil, the purpose of this study was to examine the sedative effects of inhaled linalool in mice. Mice were placed in an inhalation chamber during 60 min, in an atmosphere saturated with 1% or 3% linalool. Immediately after inhalation, animals were evaluated regarding locomotion, barbiturate-induced sleeping time, body temperature and motor coordination (rota-rod test). The 1% and 3% linalool increased (p<0.01) pentobarbital sleeping time and reduced (p<0.01) body temperature. The 3% linalool decreased (p<0.01) locomotion. Motor coordination was not affected. Hence, linalool inhaled for 1h seems to induce sedation without significant impairment in motor abilities, a side effect shared by most psycholeptic drugs.

Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice

Aromatherapy uses essential oils (EOs) for several medical purposes, including relaxation. The association between the use of aromas and a decrease in anxiety could be a valuable instrument in managing anxiety in an ever increasing anxiogenic daily life style. Linalool is a monoterpene commonly found as the major volatile component of EOs in several aromatic plant species. Adding to previously reported sedative effects of inhaled linalool, the aim of this study was to investigate the effects of inhaled linalool on anxiety, aggressiveness and social interaction in mice. Additionally, we investigated the effects of inhaled linalool on the acquisition phase of a step-down memory task in mice. Inhaled linalool showed anxiolytic properties in the light/dark test, increased social interaction and decreased aggressive behavior; impaired memory was only seen the higher dose of linalool. These results strengthen the suggestion that inhaling linalool rich essential oils can be useful as a mean to attain relaxation and counteract anxiety.

Analgesic activity of Psychotria colorata (Willd. ex R. & S.) Muell. Arg. alkaloids

An ethnopharmacological survey showed that home remedies prepared with flowers, fruits and roots of Psychotria colorata (Wild. ex R. & S.) Muell. Arg. (RUBIACEAE) are used by Amazonian caboclos as pain killers. These data led to the evaluation of analgesic activity of extracts of P. colorata, using the formalin, writhing and tail-flick methods. This paper reports the Naloxone reversible opioid-like analgesic activity of alkaloids present in leafs and flowers of P. colorata.

Chronically administered guanosine is anticonvulsant, amnesic and anxiolytic in mice

Acute administration of intraperitoneal and oral guanosine has been shown to prevent quinolinic acid and alpha-dendrotoxin-induced seizures in rats and mice. In this study, we investigated the effects of 2 weeks ad libitum consumption of guanosine (0.5 mg/ml) added to mice water supply on seizures and lethality induced by the alpha-dendrotoxin, hole-board behavior, inhibitory avoidance task, locomotor activity, motor coordination, rectal temperature, body weight, and water and food consumption. Guanosine prevented seizures in 40% and death in 50% on mice treated with i.c.v. alpha-dendrotoxin; it also impaired inhibitory avoidance memory and increased head-dipping behavior and locomotor activity on the hole-board test. Guanosine consumption did not alter any of the other parameters evaluated. The anticonvulsant, amnesic, and anxyolytic-like effects may be associated with the ability of guanosine in modulating the glutamatergic excitatory system. Adding to previously reported data, these findings suggest a potential role for chronic guanosine in the management of diseases associated with glutamatergic excitotoxicity, including epilepsy and anxiety.

Beta-endorphin causes retrograde amnesia and is released from the rat brain by various forms of training and stimulation

The endogenous opiate peptide, beta-endorphin (0.4, 1.0, 2.0, and 10.0 μg/kg) was injected IP into rats immediately after training in a shuttle avoidance task, and its effect on memory retention was evaluated in test sessions carried out 24 h later. The drug was found to cause retrograde amnesia, the ED50 being 1.0 μg/kg. Beta-endorphin immunoreactivity was measured in the hypothalamus and rest of the brain of rats submitted to training, or test sessions of shuttle avoidance learning, pseudoconditioning in the shuttle-box, tones alone, or foot-shocks alone. After training in any of the four paradigms, there was a marked (46–60%) depletion of beta-endorphin immunoreactivity in the rest of the brain. No changes were detected in the hypothalamus or after test sessions. The loss of beta-endorphin immunoreactivity may be attributed to release of this substance caused by the stimuli used for training. From the present findings, as well as previous observations on the memory-facilitating influence of the opiate receptor antagonist, naloxone, it is concluded that there is a physiological amnesic mechanism mediated by beta-endorphin (and perhaps other opoid peptides as well), which is triggered by the non-associative factors present in the various forms of learning.

Antidepressant-like effects of melatonin in the mouse chronic mild stress model.

Melatonin is a hormone primarily synthesized by the pineal gland and has been shown to govern seasonal and circadian rhythms, as well as the immune system, certain behaviours, and responses to stress. Chronic exposure to stress is involved in the etiology of human depression, and depressed patients present changes in circadian and seasonal rhythms. This study investigated the effects of daily exogenous melatonin (1 and 10 mg/kg, p.o.) and imipramine (20 mg/kg, i.p.) on the changes in the coat state, grooming behaviour and corticosterone levels induced by the unpredictable chronic mild stress model of depression in mice. As expected, the 5 weeks of unpredictable chronic mild stress schedule induced significant degradation of the coat state, decreased grooming and increased serum corticosterone levels. All of these unpredictable chronic mild stress-induced changes were counteracted by melatonin (P<0.05) and imipramine (P<0.01). Especially in view of the relevance of stress as a major contributing factor in depression, as well as the alleged importance of normalizing a hyperfunctioning HPA axis and resynchronizing circadian rhythms for a successful treatment of depression, this study reassesses the potential of melatonin as an antidepressant.

Effects of linalool on glutamate release and uptake in mouse cortical synaptosomes

Linalool, a monoterpene compound prevalent in essential oil of plant species traditionally used as sedatives, has been characterized as anticonvulsant in several experimental models. Linalool inhibits the binding of [3H]glutamate and [3H]dizocilpine to brain cortical membranes, indicating a participation of the glutamatergic transmission its mechanism of action. In this study, we investigated the effects of linalool on [3H]glutamate release (basal and potassium-stimulated) and [3H]glutamate uptake in mice cortical synaptosomes. Linalool significantly reduced potassium-stimulated glutamate release as well as glutamate uptake, not interfering with basal glutamate release. The data indicates that linalool may interfere with several relevant elements of the glutamatergic transmission, including detriment of the K+-stimulated glutamate release.

Post-training intraperitoneal administration of Leu-enkephalin and β-endorphin causes retrograde amnesia for two different tasks in rats

The immediate post-training administration of Leu-enkephalin or of β-endorphin (10 μg/kg, ip) in rats causes retrograde amnesia, both for the habituation of a rearing response to a tone, and for shuttle avoidance behavior. The facts that the doses employed were very low, and that in previous papers the opiate antagonist, naloxone, was found to have an opposite effect, suggest that endogenous opiates are physiologically active amnesic agents.