RESUMO
It is known that (-)-linalool is a competitive antagonist of NMDA receptors, which play a key role in the learning and memory processes; however, only a few studies have reported a possible interference of (-)-linalool in memory. The purpose of this study was to investigate the (-)-linalool effects on acquisition of short- and long-term memories through the objects recognition task, inhibitory avoidance test and habituation to a novel environment. Furthermore, the open field test was used to investigate the interference of (-)-linalool in motivation, locomotion and exploration by animals. Wistar male adult rats received an intraperitoneal injection (i.p.) of saline (NaCl 0.9%), tween 5% or (-)-linalool (50 or 100 mg/kg) before training in the tasks; MK-801 (0.1 mg/kg), a glutamate antagonist, was used as positive control. Short-term (STM) and long-term (LTM) memories were tested 1.5 and 24 h after training, respectively, in the inhibitory avoidance and recognition objects. The results suggested that (-)-linalool (as 50- and 100-mg/kg doses) impaired LTM acquisition, but not STM acquisition, in the object recognition task. In the inhibitory avoidance test, animals receiving linalool (both doses) showed impairment in acquisition of both memories measured. In the open field test, the animals that received (-)-linalool showed no significant difference in the crossings and latency to start the locomotion in any of the doses tested, although (-)-linalool 100 mg/kg reduced rearing behavior. When re-exposed to open field 24 h after training, the rats that received (-)-linalool 100mg/kg showed no habituation. Taken together, these data suggested that (-)-linalool was able to impair the acquisition of memory in rats, which can be associated to (-)-linalool antagonist capacity as regards NMDA glutamatergic receptors, since other glutamate antagonists also seem to affect memory.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Habituação Psicofisiológica/efeitos dos fármacos , Memória/efeitos dos fármacos , Monoterpenos/farmacologia , Monoterpenos Acíclicos , Análise de Variância , Animais , Maleato de Dizocilpina/farmacologia , Inibição Psicológica , Masculino , Monoterpenos/administração & dosagem , Preparações de Plantas/farmacologia , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
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.
Assuntos
Córtex Cerebral/metabolismo , Ácido Glutâmico/metabolismo , Monoterpenos , Sinaptossomos/efeitos dos fármacos , Terpenos/farmacologia , Monoterpenos Acíclicos , Animais , Córtex Cerebral/citologia , Córtex Cerebral/enzimologia , L-Lactato Desidrogenase/metabolismo , Masculino , Camundongos , Sinaptossomos/enzimologia , Sinaptossomos/metabolismoRESUMO
Linalool is a monoterpene compound reported to be a major component of essential oils of several aromatic species. Several linalool-producing species are used in traditional medical systems for sedative purposes, including the interruption and prevention of seizures. Previous studies in mice revealed that linalool modulates glutamatergic (competitive antagonism of L-[(3)H]glutamate binding, delayed intraperitoneal NMDA-induced convulsions and blockade of intracerebroventricular Quin-induced convulsions) and GABAergic transmission (protection against pentylenetetrazol and picrotoxin-induced convulsions). To further clarify the anticonvulsive mechanisms of linalool, we studied the effects of linalool on binding of [(3)H]MK801 (NMDA antagonist) and [(3)H]muscimol (GABA(A) agonist) to mouse cortical membranes. Linalool showed a dose dependent non-competitive inhibition of [(3)H]MK801 binding (IC(50) = 2.97 mM) but no effect on [(3)H]muscimol binding. The data suggest that the anticonvulsant mode of action of linalool includes a direct interaction with the NMDA receptor complex. The data do not, however, support a direct interaction of linalool with GABA(A) receptors, although changes in GABA-mediated neuronal inhibition or effects on GABA release and uptake cannot be ruled out.
Assuntos
Anticonvulsivantes/farmacologia , Encéfalo/efeitos dos fármacos , Maleato de Dizocilpina/farmacocinética , Agonistas GABAérgicos/farmacocinética , Monoterpenos , Muscimol/farmacocinética , Plantas Medicinais , Receptores de N-Metil-D-Aspartato/agonistas , Terpenos/farmacologia , Monoterpenos Acíclicos , Animais , Masculino , Camundongos , Óleos de Plantas/farmacologia , TrítioRESUMO
Chronic in vivo models of epilepsy provide a suitable strategy for quantifying epileptogenesis, as well as investigating neurochemical changes associated with neuronal plasticity that leads to seizuring conditions. The aim of this paper was to investigate antiepileptogenic properties of phenobarbital, focusing on the neurochemical changes associated with repeated seizures induced by low convulsive dose of pentylenetetrazol (PTZ) (60 mg/kg, sc) in mice. Phenobarbital (10 and 30 mg/kg, ip) significantly diminished the severity of seizures induced by PTZ. Repeated PTZ administration was associated with an increase in [3H]glutamate binding (B(max) 196.6+/-10.2 pmol/mgxcontrol B(max) 137.7+/-17.0 pmol/mg). Regarding NMDA receptors, repeated PTZ administration was likewise associated with an increase in [3H]MK-801 binding (0.55+/-0.02 pmol/mgxcontrol 0.32+/-0.01 pmol/mg). In addition, phenobarbital (10 mg/kg) prevented the increase in [3H]glutamate binding (B(max) 133.7+/-11.4 pmol/mg), as well as in [3H]MK-801 binding (phenobarbital 10 and 30 mg/kg, 0.33+/-0.01 and 0.34+/-0.01 pmol/mg, respectively). This study reveals an interesting capability of phenobarbital in interfering with the establishment of both the behavioral expression and associated neurochemical changes induced by the repeated administration of low convulsive dose of PTZ, which may be important in the context of preventing epileptogenesis.
Assuntos
Anticonvulsivantes/uso terapêutico , Fenobarbital/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/metabolismo , Córtex Cerebral/metabolismo , Convulsivantes , Maleato de Dizocilpina/metabolismo , Antagonistas de Aminoácidos Excitatórios/metabolismo , Ácido Glutâmico/metabolismo , Masculino , Camundongos , Pentilenotetrazol , Fenobarbital/metabolismo , Convulsões/induzido quimicamente , Convulsões/metabolismoRESUMO
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.