5-HT2 receptor activation in the midbrain periaqueductal grey (PAG) reduces anxiety-like behaviour in mice

It is widely acknowledged that the indoleamine neurotransmitter serotonin (5-HT) plays a dual role in the regulation of anxiety, a role that in part depends upon neuroanatomical locus of action. Thus, whereas stimulation of 5-HT1A or 5-HT2 receptors in the limbic forebrain (amygdala, hippocampus) enhances anxiety-like responding in rodents, activation of corresponding receptor populations in the midbrain periaqueductal grey (PAG) more often than not reduce anxiety-like behaviour. The present study specifically concerns the anxiety-modulating influence of 5-HT2 receptors within the mouse PAG. Experiment 1 assessed the effects of intra-PAG infusions of the 5-HT2B/2C receptor agonist mCPP (0, 0.03, 0.1 or 0.3 nmol/0.1 mu l) on the behaviour of mice exposed to the elevated plus-maze. As mCPP acts preferentially at 5-HT2B and 5-HT2C receptors, Experiment 2 investigated its effects in animals pretreated with ketanserin, a preferential 5-HT2A/2C receptor antagonist. In both cases, test sessions were videotaped and subsequently, scored for anxiety-like behaviour (e.g., percentage of open arm entries and percentage of open arm time) as well as general locomotor activity (closed arm entries). The results of Experiment I showed that mCPP microinfusions (0.03 and 0.1 nmol) into the PAG of mice decreased behavioural indices of anxiety without significantly altering general activity measures. In Experiment 2, the anxiolytic-like profile of intra-PAG mCPP (0.03 nmol) was substantially attenuated by intra-PAG pretreatment with an intrinsically inactive dose of the preferential 5-HT2A/2C receptor antagonist, ketanserin (10 nmol/0.1 mu l). Together, these data suggest that 5HT(2C) receptor populations within the midbrain PAG play an inhibitory role in plus-maze anxiety in mice. (C) 2007 Elsevier B.V. All rights reserved.

Social defeat stress in rats: escalation of cocaine and speedball binge self-administration, but not heroin

Exposure to intermittent episodes of social defeat stress can increase drug seeking and leads to intense drug taking in rats.This study investigated the consequences of repeated, intermittent social defeat stress on patterns of drug self-administration in rats with access to heroin, cocaine, or a heroin-cocaine combination (speedball).Male Long-Evans rats were either handled (controls) or subjected to 25-min social defeat stress episodes on days 1, 4, 7, and 10 during confrontations with an aggressive resident. Ten days following the last defeat, rats were assessed for locomotor cross-sensitization in response to heroin or cocaine. Animals were then prepared with intrajugular catheters for drug self-administration. Separate groups of controls and defeated rats were examined for self-administration of heroin (experiment 1), a heroin-cocaine combination (experiment 2), or cocaine (experiment 3). Drug self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement during limited access sessions or a 24-h unlimited access binge.Rats with a history of intermittent social defeat stress showed sensitized locomotor behavior when challenged with heroin or cocaine relative to controls. During the 24-h binge session, defeated rats escalated cocaine-taking behavior (ca. 110 mg/kg vs. 66 mg/kg in controls), persisted in self-administering cocaine or the heroin-cocaine mixture for more hours, and showed a tendency for increased heroin-cocaine intake, but no effects on heroin taking.A history of social defeat stress seems to preferentially promote escalated intake of cocaine but not heroin, unless a heroin-cocaine combination is available.

Exposição repetida à cafeína aumenta a atividade locomotora induzida pelo femproporex em ratos adolescentes e adultos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of cocaine on periadolescent rats with or without early maternal separation

Cocaine-induced behavioral sensitization and weight loss were investigated in periadolescent Wistar rats kept with their mothers or subjected to repeated maternal separation. Litters allocated to the separation procedure were placed in a temperature-controlled (33ºC) chamber for 3 h per day from postnatal day 6 (P6) to P20. Non-handled rats were left undisturbed until weaning. Treatments were started on P30-31 and the test was performed on P36-37. Animals received injections of saline or cocaine (10 mg/kg, sc) twice daily for 5 days. on day 6 all animals received saline. on day 7 animals were challenged with 10 mg/kg cocaine and their locomotion was evaluated in activity cages. A third group received saline throughout the 7-day period. Body weights were recorded on P30-31 and P36-37. Two-way ANOVA on body weights showed a main effect of treatment group (F(1,35) = 10.446, P = 0.003; N = 10-12). Non-handled rats treated with cocaine for 5 days gained significantly less weight, while no significant effect was observed in maternally separated rats. Two-way ANOVA revealed a main effect of drug treatment on locomotor activity (F(2,32) = 15.209, P<0.001; N = 6-8), but not on rearing condition (F(1,32)<0.001, P = 0.998). Animals pretreated with cocaine showed a clear behavioral sensitization relative to the saline group. No difference in the magnitude of sensitization was found between separated and non-handled animals. Only the effect of cocaine on weight gain was significantly affected by repeated episodes of early maternal separation during the pre-weaning period.

Cocaine-induced behavioral sensitization in adolescent rats endures until adulthood: Lack of association with GluR1 and NR1 glutamate receptor subunits and tyrosine hydroxylase

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Amphetamine- and nicotine-induced cross-sensitization in adolescent rats persists until adulthood

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stress-induced cross-sensitization to amphetamine is related to changes in the dopaminergic system

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Behavioral and neuroendocrine effects of the exposure to chronic restraint or variable stress in early adolescent rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stress induces behavioral sensitization, increases nicotine-seeking behavior and leads to a decrease of CREB in the nucleus accumbens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Time course of training-induced microcirculatory changes and of vegf expression in skeletal muscles of spontaneously hypertensive female rats

Exercise-induced vessel changes modulate arterial pressure (AP) in male spontaneously hypertensive rats (SHR). Vascular endothelial growth factor (VEGF) is important for angiogenesis of skeletal muscle. The present study evaluated the time course of VEGF and angiogenesis after short- and long-term exercise training of female SHR and Wistar Kyoto (WKY) rats, 8-9 weeks (200-250 g). Rats were allocated to daily training or remained sedentary for 3 days (N = 23) or 13 weeks (N = 23). After training, the carotid artery was catheterized for AP measurements. Locomotor (tibialis anterior and gracilis) and non-locomotor skeletal muscles (temporalis) were harvested and prepared for histologic and protein expression analyses. Training increased treadmill performance by all groups (SHR = 28%, WKY = 64%, 3 days) and (SHR = 141%, WKY = 122%, 13 weeks). SHR had higher values of AP than WKY (174 ± 4 vs 111 ± 2 mmHg) that were not altered by training. Three days of running increased VEGF expression (SHR = 28%, WKY = 36%) simultaneously with an increase in capillary-to-fiber ratio in gracilis muscle (SHR = 19%, WKY = 15%). In contrast, 13 weeks of training increased gracilis capillary-to-fiber ratio (SHR = 18%, WKY = 19%), without simultaneous changes in VEGF expression. Training did not change VEGF expression and capillarity of temporalis muscle. We conclude that training stimulates time- and tissue-dependent VEGF protein expression, independent of pressure levels. VEGF triggers angiogenesis in locomotor skeletal muscle shortly after the exercise starts, but is not involved in the maintenance of capillarity after long-term exercise in female rats.

Influência da adição de carga na marcha em esteira de crianças com paralisia cerebral hemiparética espástica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Parametric analyses of anxiety in zebrafish scototaxis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação comportamental e neuroquímica de ratos em dessincronização forçada: possíveis implicações para um modelo animal de oscilações no humor

Bipolar disorder has been growing in several countries. It is a disease with high mortality and has been responsible by the social isolation of the patients. Bipolar patients have alterations in circadian timing system, showing a phase shift in various physiological variables. There are several arguments demonstrating alterations in circadian rhythms may be part of the bipolar disorder pathophysiology. Given the necessity for further elucidation, the goal of this study was to validate the forced desynchronization protocol as an animal model for bipolar disorder. To do this, Wistar rats were submitted to a forced desynchronization protocol which consists in a symmetrical light dark cycle with 22h. Under this protocol, rats dissociate the locomotor activity rhythm into two components: one synchronized to the light / dark cycle with 22h, and another component with period longer than 24 hours following the animal endogenous period. These rhythms with different periods sometimes there is coincidence, which we named CAP (Coincidence Active Phase) and the opposite phase, non-coincidence, called NCAP (Non-Concidence Active Phase). The hypothesis is that in CAP animals present a mania-like behavior and animals in NCAP depressive-like behavior. We found some evidence described in detail throughout this thesis. In sum, the animals under forced desynchronization protocol were more stressed, showed an increase in stereotypic behaviors such as grooming and reduction in other behaviors such as risk assessment and vertical exploration when compared to the control group. The CAP animals showed increased locomotor activity, especially during the dark phase when compared to controls (rats under T24) and less depressive behavior in the forced swim test. The animals in NCAP showed a higher anxiety in elevated plus maze, but they don t have ahnedonia. The animals under dissociation have more labeled 5HT1A cells at the amygdala area, which appoint that they have more amygdala inhibition. Taking these data together, we could partially validated the forced desynchronization protocol as an animal model for mood oscillations

Efeitos da cafeína sobre a memória de saguis (Callithrix jacchus)

Caffeine is considered the most consumed psychostimulant in the world, presenting several central and peripheral effects. In the Central Nervous System the major effect occur by its antagonistic activity at the A1 and A2a subtypes of the adenosine receptors. These receptors are responsible for the slow-wave sleep induction, and their binding, caused by the consumption of foods and beverages that contain caffeine, cause behaviors like increase of alertness, mood and locomotion. The effects of caffeine on memory are still discussed because of the diversity of experimental protocols. Also, it does not have the same effects on all stages of the processing of memory - acquisition, consolidation and recall. Thus, using the marmoset (Callitrhix jacchus) as subject, we aim to evaluate the effects of caffeine on the memory of this primate through the conditioned place preference paradigm, where the animal selects a context by presence of food. This cognitive task consists of five phases. The first phase was two sessions of pre-exposure, in which they were evaluated for preference for any compartment of the apparatus. Then, we proceeded the training, conditioning the animals to the food-present context for 8 days. Then, there was administration of caffeine or placebo (10mg/kg) for 8 consecutive days, during the pre-sleep phase, where the 20 animals were distributed in two groups: placebo and repeated. The forth phase was one day of retraining, a re-exposure of the apparatus to the marmosets followed by the administration of caffeine (for the repeated group and a new group called abstinence) or placebo (for placebo and abstinence groups). Finally, was the test where we evaluated if the subjects learned where the food was present. Moreover, in this work we evaluate the existence of differences between females and males on the task, and the locomotor activity for the experimental groups. The results showed that in the pre-exposure phase the animals were habituated on the apparatus and did not present differences for any contexts. In training, they were able to learn the conditioning task, independent of gender. For the retraining, the two groups exhibited more interactions in rewarded context than that in non-rewarded context. Nevertheless, in the locomotor activity, the repeated group moved similarly in contact with the apparatus and outside of it. In the other hand, the animals of the placebo group moved more when in contact with the apparatus. In the test phase, the marmosets under influence of caffeine presented an increase in the locomotor activity when compared with the placebo group, corroborating works that show this increase in locomotion. In the learning evaluation, the continuous and abstinence groups had a bad performance in the task in relation to the placebo and acute groups. This suggests that the prolonged administration of caffeine disrupts the memories because it affected sleep, which is largely responsible offline processing of memories