Effect of a lavender essential oil and sleep hygiene protocol on insomnia in postmenopausal women: A pilot randomized clinical trial.

INTRODUCTION: Insomnia and vasomotor symptoms are frequently experienced during the menopausal transition and in postmenopause, worsening sleep maintenance and quality of life. Our study evaluated the use of lavender essential oil and sleep hygiene guidance on quality of life, sleep patterns and self-reported hot flashes in postmenopausal women with insomnia diagnosis. METHODS: This study is part of a larger experimental, double-blind, randomized controlled trial. We included 35 postmenopausal women with a diagnosis of insomnia who were distributed in two groups: A Placebo group (sunflower oil) and an Aroma group (Lavandula angustifolia essential oil); both inhaled the oils before bedtime for 29 days. The groups received sleep hygiene guidelines and weekly follow-up. Validated questionnaires were used to assess the effect of the intervention, and a sleep diary was used to assess sleep onset latency (SOL), total sleep time (TST), and sleep efficiency (SE) daily. Participants who complained of vasomotor symptoms at baseline kept a daily record of their frequency and intensity. RESULTS: All participants benefited in almost all domains of quality of life and in the self-assessed TST and SE. The Aroma group achieved a significant improvement in their overall quality of life score over time. No differences were observed in respect of the hot flashes record and daytime sleepiness. CONCLUSIONS: The aromatherapy intervention was effective in improving the overall quality of life in the Aroma group. Moreover, the sleep diary and sleep hygiene instructions helped all participants to, respectively, self-assess and improve their sleep patterns.

Memory reactivation mediates emotional valence updating of contextual memory in mice with protracted morphine withdrawal.

Mice subjected to morphine locomotor sensitization develop increased anxiety-behavior expression during protracted morphine withdrawal. This behavioral change is dependent on reexposure to the context of locomotor sensitization and reflects a state of conditioned anxiety. In this study, the effect of memory reconsolidation on the expression of conditioned anxiety in mice with protracted morphine withdrawal was examined. Five experimental protocols involving male C57BL/6 mice were used in which the animals were subjected to locomotor sensitization induced by morphine and reexposed to the context associated with the drug effect 28 days after locomotor sensitization and immediately after subjected to elevated plus maze. In experiment 1, mice were subjected or not to memory reactivation session and was observed that memory reactivation 27 days after sensitization reduced conditioned anxiety. In experiment 2, mice were subjected to memory reactivation, 24 h, 6 h or 1 h before contextual reexposure, and the effect of memory reactivation coincided with the temporal requirement for reconsolidation. In experiment 3, which involved exposure to a situation of acute stress immediately before memory reactivation, the mice demonstrated a return to increased conditioned anxiety. To confirm the influence of reconsolidation, in experiments 4 and 5, mice subjected to memory reactivation were treated with Nimodipine, diazepam or cyclohexamine, substances commonly used as pharmacological controls in reconsolidation experiments. Treatment with each substance separately inhibited the effect of reactivation in experiment 5 (presence of acute stressor) but not in experiment 4 (absence of acute stressor). These results suggest that, in our experimental model, reconsolidation is mediated through updating of the emotional valence of contextual memory associated with the administration of morphine.

Lavender essential oil on postmenopausal women with insomnia: Double-blind randomized trial.

BACKGROUND: To evaluate the effect of Lavandula angustifolia essential oil inhalation on sleep and menopausal symptoms in postmenopausal women with insomnia. PARTICIPANTS: 35 postmenopausal women with a clinical diagnosis of insomnia were included, 17 in Aroma Group (AG) and 18 in Placebo Group (PG). METHODS: In this double-blind, randomized controlled trial, PG participants inhaled sunflower oil and AG participants inhaledLavandula angustifolia essential oil, for 29 days. Both groups received sleep hygiene guidelines before the intervention and weekly follow-up during it. Evaluations were performed before and after intervention. All statistical analyses and intention-to-treat test were performed in SPSS 22. Sleep quality (Primary outcome) was measured by Pittsburgh Sleep Quality Index. Secondary outcomes were polysomnography data, severity of insomnia, anxiety and depression symptoms, and postmenopausal symptoms. RESULTS: There were no significant differences between groups after intervention in the primary outcome (P = 0.22; effect size=0.69); however, a tendency of improvement in wake after sleep onset (WASO) was observed (P = 0.07; effect size=0.81; B = 42.2). Both groups presented better sleep quality over time (AG P < 0.001; PG P = 0.011). AG participants showed a significant decrease in sleep onset latency (P = 0.001), depression levels (P = 0.025), hot flashes (P < 0.001), postmenopausal symptoms (P < 0.001) and, in polysomnography data, increased sleep efficiency (P = 0.002) compared to baseline. CONCLUSION: Although no significant differences were observed between groups, our data presented a tendency of improvement in WASO. Moreover, AG participants had enhanced overall sleep pattern, quality and sleep efficiency. Weekly follow-up and sleep hygiene instructions were essential for both groups to show improvement in almost all outcomes. CLINICAL TRIAL REGISTRATION: Brazilian Registry of Clinical Trials, www.ensaiosclinicos.gov.br, RBR-5q5t5z.

Inhaled Lavandula angustifolia essential oil enhances extinction learning and inhibits memory updating in mice submitted to the contextual fear conditioning.

ETHNOPHARMACOLOGICAL RELEVANCE: Lavender (Lavandula angustifolia) essential oil (EO) has a long history of use in emotional illness, including anxiety disorders. Cognitive mechanisms of learning and memory play a pivotal role in the etiology and maintenance of anxiety since exposure to cues related to aversive situations induces high arousal and anticipatory anxiety. Memory become labile after its reactivation and can be modulated by reconsolidation or extinction. Inhibition of memory reconsolidation or facilitation of memory extinction may be effective in preventing or minimizing the effect of contextual cues on anticipatory anxiety. AIM OF THE STUDY: We investigated the effect of Lavandula angustifolia EO in the memory updating of conditioned contextual fear. MATERIALS AND METHODS: Adult male C57Bl6 mice were submitted to fear conditioning. Two days after conditioning the mice underwent a reactivation session in a hybrid context and were then immediately exposed to vaporized water or essential oil at concentrations of 1%, 2.5% or 5% for 3 h. Two days later, the mice were tested in the original or an altered context and their freezing behavior was measured. In addition, mice were subjected to a fear memory recovery protocol followed by a reinstatement session. RESULTS: In the contextual fear test, 1% essential oil, but not 2.5% or 5%, reduced the freezing behavior response, whereas after a reinstatement session, exposure to 1% essential oil increased the freezing behavior response. CONCLUSIONS: These results suggest that Lavandula angustifolia essential oil enhances memory extinction and, consequently, inhibits memory updating.

Anxiety-like behavior in acute and protracted withdrawal after morphine-induced locomotor sensitization in C57BL/6 male mice: The role of context.

Contextual memory plays an important role in development and maintenance of drug addiction. However, little is known about of the role contextual memory in the emergence of a negative emotional state in the withdrawal period. Therefore, this study investigated anxiety-like behavior in acute and protracted morphine withdrawal of mice submitted to a locomotor sensitization protocol and the influence of contextual memory on this behavior. Male adult C57Bl6 mice were subjected to morphine locomotor sensitization and anxiety-like behavior was assessed by using the elevated plus maze test (EPM). To evaluate associative memory, the mice were re-exposed to the context of locomotor sensitization immediately before EPM. As expected, repeated morphine administrations promoted locomotor sensitization, seen as a gradual increase in the distance traveled during the acquisition phase. There was an increase in anxiety-like behavior upon acute withdrawal, as indicated by a decrease in open arms activity (OAA), but this effect dissipated over time. However, when the context was presented, mice in protracted withdrawal showed enhanced anxiety-like behavior, indicated by an increase in closed arms activity (CAA). This effect was context specific since re-exposure in an alternative context did not change the anxiety-like behavior. Treatment with diazepam counteracted the decrease in OAA in acute withdrawal and the increase in CAA induced by context re- exposure during protracted abstinence. Thus, repeated morphine administration induced a negative emotional state when the drug was discontinued. The context associated with drug exposure played a pivotal role in the appearance of anxiety-like behavior, even long after drug discontinuation. There were differences in the patterns of anxiety behaviors in acute (unconditioned anxiety-like behavior) and protracted (conditioned anxiety-like behavior) withdrawal since the former was characterized by a passive behavioral strategy and the latter by an active behavioral strategy.

Inhaled Lavandula angustifolia essential oil inhibits consolidation of contextual- but not tone-fear conditioning in rats.

Although the current treatment for anxiety is effective, it promotes a number of adverse reactions and medical interactions. Inhaled essential oils have a prominent action on the central nervous system, with minimal systemic effects, primarily because of reduced systemic bioavailability. The effects of drugs on the consolidation of fear conditioning reflects its clinical efficacy in preventing a vicious cycle of anticipatory anxiety leading to fearful cognition and anxiety symptoms. In this study, we investigated the effects of inhaled Lavandula angustifolia essential oil on the consolidation of aversive memories and its influence on c-Fos expression. Adult male Wistar rats were subjected to a fear conditioning protocol. Immediately after the training session, the rats were exposed to vaporized water or essential oil (1%, 2.5% and 5% solutions) for 4h. The next day, the rats underwent contextual- or tone-fear tests and 90min after the test they were euthanized and their brains processed for c-Fos immunohistochemistry. In the contextual-fear test, essential oil at 2.5% and 5% (but not 1%) reduced the freezing response and its respective c-Fos expression in the ventral hippocampus and amygdala. In the tone-fear test, essential oil did not reduce the freezing response during tone presentation. However, rats that inhaled essential oil at 2.5% and 5% (but not 1%) showed decreased freezing in the three minutes after tone presentation, as well as reduced c-Fos expression in the prefrontal cortex and amygdala. These results show that the inhalation of L. angustifolia essential oil inhibited the consolidation of contextual- but not tone-fear conditioning and had an anxiolytic effect in a conditioned animal model of anxiety.

Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference.

Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice. Using a novel sensitive RNAscope in situ hybridization, we detected CB2R mRNA expression in VTA DA neurons in wildtype and DAT-Cnr2 cKO heterozygous but not in the homozygous DAT-Cnr2 cKO mice. Here we report that the deletion of CB2Rs in dopamine neurons enhances motor activities, modulates anxiety and depression-like behaviors and reduces the rewarding properties of alcohol. Our data reveals that CB2Rs are involved in the tetrad assay induced by cannabinoids which had been associated with CB1R agonism. GWAS studies indicates that the CNR2 gene is associated with Parkinson's disease and substance use disorders. These results suggest that CB2Rs in dopaminergic neurons may play important roles in the modulation of psychomotor behaviors, anxiety, depression, and pain sensation and in the rewarding effects of alcohol and cocaine.

Evidence of memory generalization in contextual locomotor sensitization induced by amphetamine.

Addiction is a multifactorial disease that comprises physiological mechanisms of learning and memory. Addict subjects have intense plasticity in cortical and limbic circuits during intoxication, abstinence or even in drug seeking behavior. Locomotor sensitization is a classic animal model of drug addiction that mimics the changes that occur in the transition from drug use to drug addiction. Several studies have demonstrated the importance of contextual associative processes in this task. However, whether the mechanisms of sensitization are maintained and precise over the time remain an open question. Thus, the aim of this study was to investigate the importance of context in the maintenance and precision of locomotor sensitization across time. For this, male c57bl/6 mice were submitted to different contexts during the acquisition phase of amphetamine-induced locomotor sensitization. We found that after 3days of withdrawal, the expression of locomotor sensitization was context dependent, as characterized by an increased locomotion in the acquisition context (A), but not in the novel context (B). Surprisingly, when the expression of locomotor sensitization was tested after 28days of withdrawal, mice that acquired sensitization in the context A exhibited increased locomotion in both contexts (A and B), suggesting that memories associated with amphetamine drugs generalize following long periods of abstinence. The same generalization did not occur in mice sensitized in a well-known context (home cage). These results demonstrate, for the first time, the influence of memory generalization in amphetamine-induced locomotor sensitization. The evidence that memory generalization also occurs in sensitization provides new advances in the comprehension of the mechanisms underlying memory role in addiction process. Elucidating the mechanisms of amphetamine sensitization may shed some light on understanding the transition from drug use to addiction.

Reconsolidation and update of morphine-associated contextual memory in mice.

Drug addiction can be viewed as a pathological memory that is constantly retrieved and reconsolidated. Since drug abuse takes place in different contexts, it could be considered that reconsolidation plays a role in memory updating. There is consistent evidence supporting the role of reconsolidation in the strength and maintenance of contextual memories induced by drugs of abuse. However, this role is not well established in memory update. The purpose of the current study was to assess the reconsolidation process over memory update. C57BL6 mice were subjected to a morphine-induced, conditioned place preference (CPP) paradigm. Based on CPP results, animals were divided into distinct experimental groups, according to the contextual characteristics of the re-exposure and a second CPP Test. Re-exposure in the original context was important for memory maintenance and re-exposure under discrete contextual changes resulted in memory updating, although original memory was maintained. Interestingly, cycloheximide, an inhibitor of protein synthesis, had different outcomes in our protocol. When the re-exposure was done under discrete contextual changes, cycloheximide treatment just after re-exposure blocked memory updating, without changes in memory maintenance. When re-exposure was done under the original context, only two subsequent cycloheximide injections (3 and 6h) disrupted later CPP expression. Considering the temporal window of protein synthesis in consolidation and reconsolidation, these findings suggest that re-exposure, according to the contextual characteristics in our protocol, could trigger both phenomena. Furthermore, when new information is present on retrieval, reconsolidation plays a pivotal role in memory updating.

Cocaine counteracts LPS-induced hypolocomotion and triggers locomotor sensitization expression.

Neuroimmune signalling underlies addiction and comorbid depression. Clinical observations indicate that infections and chronic lesions are more frequent in drug users and elevated inflammatory states are evident in cocaine dependents. Therefore, lipopolysaccharide (LPS) and inflammatory cytokines represent an important tool for the investigation of sickness, depressive illness and addiction behaviour. A major component of addiction is the progressive and persistent increase in locomotor activity after repeated drug administration and even prolonged periods of abstinence. The aim of this study was to investigate the response of locomotor sensitization when a non-sensitizing dose of cocaine is paired with a systemic inflammatory stimulus. LPS and cocaine were administered intraperitonealy in young-adult male C57bl/6 mice during a 5-day acquisition phase. After a 48-h withdrawal period all groups were challenged with cocaine to evaluate locomotor expression. During the acquisition phase, the LPS-treated groups displayed characteristic hypolocomotion related to sickness behaviour. The low dose of cocaine did not increase the distance travelled, characterizing a non-sensitization dose. Groups that received both LPS and cocaine did not display hypolocomotion, indicating that cocaine might counteract hypolocomotion sickness behaviour. Moreover, during challenge, only these animals expressed locomotor sensitization. Our results indicate that LPS could facilitate the expression of locomotor sensitization in mice and that the immune system may modulate cocaine-induced sensitization.

Chronic light deprivation inhibits appetitive associative learning induced by ethanol and its respective c-Fos and pCREB expression.

To address the role of mixed anxiety/mood disorder on appetitive associative learning, we verify whether previous chronic light deprivation changes ethanol-induced conditioned place preference and its respective expression of c-Fos and pCREB, markers of neuronal activity and plasticity. The experimental group was maintained in light deprivation for 24 h for a period of 4 wk. Subsequently, it was adapted to a standard light-dark cycle for 1 wk. As a control, some mice were maintained in standard cycle for a period of 4 wk (Naïve group). Then, all animals were submitted to behavioral tests to assess emotionality: elevated plus maze; open field; and forced swim. After that, they were submitted to ethanol-induced conditioned place preference. Ninety minutes after the place preference test, they were perfused, and their brains processed for c-Fos and pCREB immunohistochemistry. Light deprivation induced anxiety-like trait (elevated plus maze), despair (forced swim), and hyperlocomotion (open field), common features seen in other animal models of depression. Ethanol-induced conditioned place preference was accompanied by increases on c-Fos and pCREB in the hippocampus, prefrontal cortex and striatum. Interestingly, mice previously submitted to light deprivation did not develop either acquisition and/or expression of ethanol-induced conditioned place preference or increases in c-Fos and pCREB. Therefore, chronic light deprivation mimics several behavioral aspects of other animal models of depression. Furthermore, it could be useful to study the neurochemical mechanisms involved in the dual diagnosis. However, given its likely deleterious effects on appetitive associative memory, it should be used with caution to investigate the cognitive aspects related to the dual diagnosis.

Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas.

To evaluate, through a systematic review of the literature, the antitumoral effects of cannabinoids on gliomas. Research included the following electronic databases: PUBMED, EMBASE, LILACS and The Cochrane Collaboration Controlled Trials Register. All published studies involving the antitumoral effects (cellular and molecular mechanisms) of cannabinoids were considered for this review. The bibliography search strategy included all publications of each of these databases until December 31, 2012. From 2,260 initially identified articles, 35 fulfilled the inclusion criteria for this review. All the studies included in this systematic review were experimental (in vivo and/or in vitro), except for one pilot clinical trial phase I/II involving humans. In all experimental studies included, cannabinoids exerted antitumoral activity in vitro and/or antitumoral evidence in vivo in several models of tumor cells and tumors. The antitumor activity included: antiproliferative effects (cell cycle arrest), decreased viability and cell death by toxicity, apoptosis, necrosis, autophagy, as well as antiangiogenic and antimigratory effects. Antitumoral evidence included: reduction in tumor size, antiangiogenic, and antimetastatic effects. Additionally, most of the studies described that the canabinnoids exercised selective antitumoral action in several distinct tumor models. Thereby, normal cells used as controls were not affected. The safety factor in the cannabinoids' administration has also been demonstrated in vivo. The various cannabinoids tested in multiple tumor models showed antitumoral effects both in vitro and in vivo. These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.

Electroacupuncture inhibits CB1 upregulation induced by ethanol withdrawal in mice.

CB1R play a role in alcohol withdrawal and in some effects of acupuncture. Interestingly, acupuncture has been used to alleviate alcohol withdrawal. Here, we investigated electroacupuncture (EA) effects during ethanol withdrawal on CB1R immunoreactivity. Male Swiss mice were daily injected with ethanol (2g/kg, i.p) (EtOH group), for 21 days. EA was performed daily during 4 days of ethanol withdrawal. The stimuli of 2 or 100 Hz were provided in two acupoints combination: Ea1 [(ST-36/Zusanli) and (PC-6/Neiguan)] or Ea2 [(DU-14/Dazhui) and (DU-20/Baihui)]. The specificity of the acupoints were assessed by the inclusion of three additional groups, Ea3 [(ST 25/Tianshu - acupoints used to other non-related disorders)], Sham1 and Sham2 (transdermic stimulation nearly to the respective acupoints). EtOH group were only handled during withdrawal and Saline group was chronically treated with Saline and handled similarly to EtOH group. One day after withdrawal the animals were perfused and their brains processed for immunohistochemistry. There was an increase of CB1R in the prefrontal cortex, striatum, hippocampus, amygdala and ventral tegmental area. The procedures used in the 2HzEa1 and 100HzEa2 groups were the most effective and specific to inhibit this CB1R upregulation. Therefore, EA inhibits CB1R upregulation seen in ethanol withdrawn mice. The specificity of acupoints stimulation depends of the encephalic nuclei, acupoints association and frequency of stimulation.

Intermittent ethanol binge exposure impairs object recognition but spares contextual and tone fear memory in adolescent rats

Adolescent brain development seems to be important for the maturation of brain structures and behavior. Intermittent binge ethanol drinking is common among adolescents, and this type of drinking can induce brain damage and cognitive deficits. In addition, emotional changes are frequently seen in alcoholics and rodents treated with ethanol. Considering the close relation between emotional arousal and cognitive responses, the present work investigates if intermittent ethanol binge exposure could differentially alter the performance of adolescent rats in aversive and non-aversive motivated tests. Male adolescent rats were submitted to ethanol treatment (2.5 or 5.0 g/Kg, o.a.) at 48-h intervals over postnatal day (PND) 30 to 60. Control animals were exposed to a similar administration protocol with saline administration. At PND61-PND63 animals were submitted to one-trial object recognition or contextual and tone fear conditioning paradigms. Binge ethanol drinking (at both 2.5 and 5.0 g/Kg) did not change freezing response in the contextual and tone fear conditioning. However, all doses impaired recognition rates 24h after training in object recognition test. In addition, despite a diminution of horizontal locomotion in the open field (only for the 5.0 g/Kg dose), no difference was detected regarding time in immobility, time in grooming and number of rearing in this paradigm. The present results show that the cognitive impairment resulting from intermittent binge ethanol exposure has a negative correlation with learning-associated emotional arousal(AU)

Intermittent ethanol binge exposure impairs object recognition but spares contextual and tone fear memory in adolescent rats

Adolescent brain development seems to be important for the maturation of brain structures and behavior. Intermittent binge ethanol drinking is common among adolescents, and this type of drinking can induce brain damage and cognitive deficits. In addition, emotional changes are frequently seen in alcoholics and rodents treated with ethanol. Considering the close relation between emotional arousal and cognitive responses, the present work investigates if intermittent ethanol binge exposure could differentially alter the performance of adolescent rats in aversive and non-aversive motivated tests. Male adolescent rats were submitted to ethanol treatment (2.5 or 5.0 g/Kg, o.a.) at 48-h intervals over postnatal day (PND) 30 to 60. Control animals were exposed to a similar administration protocol with saline administration. At PND61-PND63 animals were submitted to one-trial object recognition or contextual and tone fear conditioning paradigms. Binge ethanol drinking (at both 2.5 and 5.0 g/Kg) did not change freezing response in the contextual and tone fear conditioning. However, all doses impaired recognition rates 24h after training in object recognition test. In addition, despite a diminution of horizontal locomotion in the open field (only for the 5.0 g/Kg dose), no difference was detected regarding time in immobility, time in grooming and number of rearing in this paradigm. The present results show that the cognitive impairment resulting from intermittent binge ethanol exposure has a negative correlation with learning-associated emotional arousal.

Staying at the crossroads: assessment of the potential of serum lithium monitoring in predicting an ideal lithium dose.

OBJECTIVE: Lithium has been successfully employed to treat bipolar disorder for decades, and recently, was shown to attenuate the symptoms of other pathologies such as Alzheimer's disease, Down's syndrome, ischemic processes, and glutamate-mediated excitotoxicity. However, lithium's narrow therapeutic range limits its broader use. Therefore, the development of methods to better predict its dose becomes essential to an ideal therapy. METHOD: the performance of adult Wistar rats was evaluated at the open field and elevated plus maze after a six weeks treatment with chow supplemented with 0.255%, or 0.383% of lithium chloride, or normal feed. Thereafter, blood samples were collected to measure the serum lithium concentration. RESULTS: Animals fed with 0.255% lithium chloride supplemented chow presented a higher rearing frequency at the open field, and higher frequency of arms entrance at the elevated plus maze than animals fed with a 50% higher lithium dose presented. Nevertheless, both groups presented similar lithium plasmatic concentration. DISCUSSION: different behaviors induced by both lithium doses suggest that these animals had different lithium distribution in their brains that was not detected by lithium serum measurement. CONCLUSION: serum lithium concentration measurements do not seem to provide sufficient precision to support its use as predictive of behaviors.

Staying at the crossroads: assessment of the potential of serum lithium monitoring in predicting an ideal lithium dose / Em uma encruzilhada: potencial do nível plasmático de lítio como preditor da dose ideal

OBJECTIVE: Lithium has been successfully employed to treat bipolar disorder for decades, and recently, was shown to attenuate the symptoms of other pathologies such as Alzheimer's disease, Down's syndrome, ischemic processes, and glutamate-mediated excitotoxicity. However, lithium's narrow therapeutic range limits its broader use. Therefore, the development of methods to better predict its dose becomes essential to an ideal therapy. METHOD: the performance of adult Wistar rats was evaluated at the open field and elevated plus maze after a six weeks treatment with chow supplemented with 0.255 percent, or 0.383 percent of lithium chloride, or normal feed. Thereafter, blood samples were collected to measure the serum lithium concentration. RESULTS: Animals fed with 0.255 percent lithium chloride supplemented chow presented a higher rearing frequency at the open field, and higher frequency of arms entrance at the elevated plus maze than animals fed with a 50 percent higher lithium dose presented. Nevertheless, both groups presented similar lithium plasmatic concentration. DISCUSSION: different behaviors induced by both lithium doses suggest that these animals had different lithium distribution in their brains that was not detected by lithium serum measurement. CONCLUSION: serum lithium concentration measurements do not seem to provide sufficient precision to support its use as predictive of behaviors.

OBJETIVO: Além de ser usado há décadas para tratar distúrbio bipolar, o lítio, mais recentemente, demonstrou-se eficaz para Alzheimer, síndrome de Down, processos isquêmicos e excitotoxicidade mediada por glutamato. Contudo, a estreita janela terapêutica do lítio limita seu uso. Portanto, o estabelecimento de métodos preditivos de dose torna-se importante. MÉTODO: O desempenho de ratos Wistar adultos foi avaliado no campo aberto e labirinto em cruz elevado após seis semanas de tratamento com uma ração suplementada com 0,255 por cento ou 0,383 por cento de cloreto de lítio ou ração normal. Coletou-se amostras de sangue para dosagem plasmática do lítio. RESULTADOS: Os animais alimentados com a ração com 0,255 por cento de cloreto de lítio fizeram mais rearing no campo aberto e tiveram uma maior freqüência de entradas nos braços do labirinto elevado que os animais que ingeriram a dose mais alta. Apesar disso, verificou-se níveis plasmáticos de lítio semelhantes em ambos os grupos. DISCUSSÃO: A variação nos comportamentos destarte a presença de níveis plasmáticos semelhantes sugere que as diferentes doses produziram diferentes concentrações cerebrais não detectadas pela medida plasmática. CONCLUSÃO: Medidas da concentração plasmática de lítio não permitem prever de forma completa seus efeitos comportamentais.

Brotamento das fibras musgosas hipocampais em epilepsia do lobo temporal: relação com aprendizagem e memória / Mossy fiber sprouting im temporal lobe epilepsy: relation to learning and memory

A ciclohexamida influencia a reorganização sináptica resultante do status epilepticus induzido por pilocarpina (SE). Para investigar possíveis conseqüências funcionais deste efeito, foi induzido SE em animais na ausência (grupo Pilo) ou presença de ciclohexamida (grupo Chx). Passados 5 ou 60 dias da indução do SE, os animais foram submetidos a diferentes testes comportamentais. Posteriormente os mesmos foram perfundidos e os encéfalos foram processados para as colorações de Neo-Timm e Cresil. Os dados apresentados neste trabalho mostraram que a administração de ciclohexamida diminuiu drasticamente a intensidade de brotamento das fibras musgosas, além de apresentar efeito neuroprotetor em algumas estruturas do lobo temporal (hilo, córtex entorrinal e córtex piriforme). Do ponto de vista comportamental, os animais epilépticos que receberam ciclohexamida mantiveram a emocional idade inalterada, enquanto que os animais epilépticos que não receberam a droga mostraram-se hiporeativos às situações estressantes (labirinto em cruz elevado e campo aberto). Contudo, não houve diferenças entre estes animais nos testes de aprendizagem e memória (labirinto aquático de Morris, condicionamento de medo ao contexto e ao som). Portanto, os resultados apresentados sugerem que a integridade de certas estruturas do lobo temporal (hilo, córtex entorrinal e córtex piriforme) é crucial para os aspectos emocionais no modelo de EL T induzido por pilocarpina. Além disso, o BFM não minimiza e nem potencializa os déficits cognitivos proporcionados pela lesão neuronal decorrente do SE induzido por pilocarpina.