Abstract Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) used in the treatment of breast cancer; however many women complain of weight gain during TAM treatment. The anorectic ...effects of estradiol (E) and TAM are well known, although the effects of E on the consumption of palatable food are controversial and there is no information regarding the effects of TAM on palatable food consumption. The aim of this study was to investigate the effects of chronic treatment with estradiol and/or tamoxifen on feeding behavior in ovariectomized rats exposed to standard chow and palatable foods (Froot Loops® or chocolate). Additionally, parameters such as body weight, uterine weight, lipid profile and plasma glucose were also measured. Wistar rats were ovariectomized (OVX) and subsequently injected (ip.) for 40 days with: E, TAM, E + TAM or vehicle (OVX and SHAM – controls). Behavioral tests were initiated 25 days after the start of treatment. Froot Loops® consumption was evaluated in a novel environment for 3 min. Standard chow intake was evaluated for two days and chocolate intake for 7 days in the home cage in a free choice model (chocolate or standard chow). Rats injected with E, TAM and E + TAM groups showed a reduction in body weight and standard chow intake, compared with control groups. With regard to palatable food intake, the E, TAM and E + TAM groups demonstrated increased consumption of Froot Loops®, compared with the SHAM and OVX groups. In contrast, all groups increased their consumption of chocolate, compared with standard chow; however the E group consumed more chocolate than the OVX, TAM and E + TAM groups. Despite these differences in chocolate consumption, all groups showed the same caloric intake during the chocolate exposure period; however the TAM and E + TAM groups presented decreased body weight. Treatment with estradiol and tamoxifen showed a favorable lipid profile with low levels of TC, LDL, LDL/HDL ratio and lower levels of plasma glucose. The E group presented high levels of TG and HDL, when compared with the TAM and E + TAM groups. Taken together, results suggest that TAM acted in an estrogen-like manner on the majority of parameters analyzed. However, tamoxifen acts in a different manner depending on the type of palatable food and the exposure. In addition, the TAM group demonstrated weight loss, compared with other groups independently of the type of food presented (palatable food or standard chow), showing a low caloric efficiency.
Abstract Anorectic effects of caffeine are controversial in the literature, while stress and obesity are growing problems in our society. Since many stressed people are coffee drinkers, the objective ...of the present study was to evaluate the effect of stress and chronic administration of caffeine on feeding behavior and body weight in male and female rats. Wistar rats (both males and females) were divided into 3 groups: control (receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated-restraint stress for 40 days). During the entire treatment, chow consumption was monitored and rats were weighed monthly. Afterwards, feeding behavior was evaluated during 3-min trials in food-deprived and ad libitum fed animals and also in repeated exposures, using palatable food (Froot Loops® and Cheetos®). Chronic administration of caffeine did not affect rat chow consumption or body weight gain, but diminished the consumption of both salty (Cheetos®) and sweet (Froot Loops®) palatable food. In the repeated trial tests, stress diminished savory snack consumption in the later exposures I.S. Racotta, J. Leblanc, D. Richard The effect of caffeine on food intake in rats: involvement of corticotropin-releasing factor and the sympatho-adrenal system. Pharmacol Biochem Behav. 1994, 48:887–892; S.D. Comer, M. Haney, R.W. Foltin, M.W. Fischman Effects of caffeine withdrawal on humans living in a residential laboratory. Exp Clin Psychopharmacol. 1997, 5:399–403; A. Jessen, B. Buemann, S. Toubro, I.M. Skovgaard, A. Astrup The appetite-suppressant effect of nicotine is enhanced by caffeine. Diab Ob Metab. 2005, 7:327–333; J.M. Carney Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats. Br J Pharmacol. 1982, 75:451–454 and caffeine diminished consumption of both palatable foods (savory and sweet) during the early and later exposures. Most responses to caffeine were stronger in females, and stress exposure influenced the effect. Neither chronic caffeine nor stress affected adrenal weight and plasma corticosterone levels of the rats. These observations suggest that chronic caffeine consumption may have sex-specific effects on palatable food ingestion.
The excitotoxicity induced by QA has been related to its ability to increase free radical content and oxidative stress. In order to investigate the time course of toxicity and oxidative profile in ...the mice hippocampus following seizures induced by QA infusion (36.8
nM, i.c.v.), we evaluated the cellular damage (PI uptake assay), content of ROS formation (DCF assay) and the total radical antioxidant potential (TRAP) and reactivity (TAR) levels. The present results showed that a cellular damage occurred as early as 4
h after QA infusion coincident with an increase in the ROS contents, which returned to control levels after 24
h, while the cellular damage persisted for 72
h. There was a marked increased in the total antioxidant capacity at 8
h after QA infusion in both reactivity and potential levels. By 72
h post-treatment, the TRAP levels decreased, but the TAR levels remained augmented. Therefore, the delayed and persistent increase in the antioxidant capacity after QA insult may be a cellular adaptative response, probably contributing to decrease the ROS levels in order to prevent the spreading of the cellular damage. Therefore, the increase in the QA level in the brain ventricle may induce oxidative stress, which is followed by a persistent response in the antioxidant system in the hippocampus. The present study may, therefore, contribute to elucidate the mechanism of the brain dysfunction in patients with several neurological disorders involving elevation of QA in the CSF.
We studied the effect of chronic caffeine on parameters related to oxidative stress in different brain regions of stressed and non-stressed rats. Wistar rats were divided into three groups: control ...(receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated restraint stress during 40 days). Lipid peroxide levels and the total radical-trapping potential were assessed, as well as antioxidant enzyme activities superoxide dismutase, gluthatione peroxidase, and catalase in hippocampus, striatum and cerebral cortex. Results showed interactions between stress and caffeine, especially in the cerebral cortex, since caffeine increased the activity of some antioxidant enzymes, but not in stressed animals. We concluded that chronic administration of caffeine led, in some cases, to increased activity of antioxidant enzymes. However, these effects were not observed in the stressed animals.
Purpose: N‐methyl d‐aspartate (NMDA) preconditioning has been used to prevent cellular death induced by glutamate or NMDA in cultured neurons. Quinolinic acid (QA)‐induced seizures are used to ...average NMDA receptors–evoked neurotoxicity in animal models. The purpose of this study was to investigate the potential neuroprotective effects of NMDA preconditioning against QA‐induced seizures and hippocampal damage in vivo.
Methods: Mice were pretreated with nonconvulsant doses of NMDA for different times before i.c.v. QA infusion and observed for the occurrence of seizures. Hippocampal slices from mice were assayed to measure cellular viability.
Results: NMDA preconditioning presented 53% protection against QA‐induced seizures, as well as QA‐induced cellular death in the hippocampus. The NMDA receptor antagonist, MK‐801, prevented the protection evoked by NMDA preconditioning. The adenosine A1 receptor antagonist, CPT, prevented the protection evoked by NMDA preconditioning against QA‐induced seizures, but not against QA‐induced hippocampal cellular damage. The adenosine A1 receptor agonist, CPA, did not mimic the NMDA preconditioning–evoked protective effects.
Conclusions: These results suggest that in vivo preconditioning with subtoxic doses of NMDA protected mice against seizures and cellular hippocampal death elicited by QA, probably through mechanisms involving NMDA receptors operating with adenosine A1 receptors.
Glutamatergic mechanisms are thought to be involved in stress-induced changes of brain function, especially in the hippocampus. We hypothesized that alterations caused by the hormonal changes ...associated with chronic and acute stress may affect glutamate uptake and release from hippocampal synaptosomes in Wistar rats. It was found that 3Hglutamate uptake and release by hippocampal nerve endings, when measured 24 h after 1 h of acute restraint, presented no significant difference. The exposure to repeated restraint stress for 40 days increased neuronal presynaptic 3Hglutamate uptake as well as basal and K+-stimulated glutamate release when measured 24 h after the last stress session. Chronic treatment also caused a significant decrease in 3Hglutamate binding to hippocampal membranes. We suggest that changes in the glutamatergic system are likely to take part in the mechanisms involved in nervous system plasticity following repeated stress exposure.
The excitatory amino acids (EAAs) transporters regulate the balance between physiological and pathological signaling over stimulation of the glutamatergic system pathway. The effect of transportable ...substrates and glutamate (Glu) receptor agonists on Glu uptake in neuronal cells was assessed at different conditions. Cells pre-incubated with Glu,
l- or
d-aspartate (Asp) and washed presented an inhibition on
3H-Glu uptake and this effect was not mimicked by Glu receptors agonists. The effects of
l- and
d-Asp were not altered by the presence of
N-methyl-
d-aspartate (NMDA) receptor antagonists. Thus, the reduction on Glu uptake induced by EAAs is probably linked to the transporter activity. In contrast, the presence of NMDA or (1
S,3
R)-1-aminocyclopentane-1,3-dicarboxylic acid (SR-ACPD) during the pre-incubation and the
3H-Glu uptake assay period increased Glu uptake, whilst kainic acid (KA) had no effect. The NMDA effect was not altered by its antagonists (±)-2-amino-5-phosphonopentanoic acid (AP-5) or dizocilpine (MK-801). The SR-ACPD effect was due to the activation of metabotropic Glu receptor, since it was abolished by its antagonist,
l(±)-2-amino-3-phosphonopropionic acid (
l-AP3). Thus, the current studies suggest that the neuronal EAAs transporter is regulated in different manner by transportable substrates and Glu receptor agonists. The possible involvement of this modulation after certain neurotoxicity insults is discussed.
Natural products, including those derived from plants, have largely contributed to the development of therapeutic drugs. Glutamate is the main excitatory neurotransmitter in the central nervous ...system and it is also considered a nociceptive neurotransmitter, by acting on peripheral nervous system. For this reason, in this study we investigated the effects of the hydroalcoholic extracts from Drymis winteri (polygodial and drimanial), Phyllanthus (rutin and quercetine), Jathopha elliptica (jatrophone), Hedyosmum brasiliense (13HDS), Ocotea suaveolens (Tormentic acid), Protium kleinii (alphabeta-amyrin), Citrus paradise (naringin), soybean (genistein) and Crataeva nurvala (lupeol), described as having antinociceptive effects, on glutamatergic transmission parameters, such as (3)Hglutamate binding, (3)Hglutamate uptake by synaptic vesicles and astrocyte cultures, and synaptosomal (3)Hglutamate release. All the glutamatergic parameters were affected by one or more of these compounds. Specifically, drimanial and polygodial presented more broad and profound effects, requiring more investigation on their mechanisms. The putative central side effects of these compounds, via the glutamatergic system, are discussed.
•Short early life stress turns animals more susceptible to psychostimulants.•Short post-weaning social isolation increases locomotor response to amphetamine.•High sugar diet prevents the social ...isolation effects on locomotor activity.•Dopaminergic parameters increase after AMPH challenge in socially isolated rats.•Chronic access to a high sugar diet does not induce dopaminergic sensitization.
Childhood and adolescence are sensitive periods of development, marked by high brain maturation and plasticity. Exposure to early life stress, such as social isolation, is able to prompt changes in sensitive brain circuitries, essentially in the mesolimbic dopaminergic system and increase the risk for addictive behaviors later in life. Post-weaning social isolation can stimulate the consumption of rewarding substances, like drugs of abuse and palatable foods. However, most studies analyze long periods of social isolation and very little is known about the effects of a brief social isolation in a sensitive period of development and its association with palatable food on the reward system sensitization. Furthermore, females are more susceptible to the reinforcing effect of drugs than males. Therefore, the aim of this study was to analyze the effects of a short post-weaning social isolation combined with a free access to a chronic high sugar diet (HSD) on the dopaminergic system, oxidative status and behavioral response to an amphetamine-like drug in adulthood. We used female Wistar rats that were socially isolated from post-natal days (PD) 21 to 35 and received free access to a HSD until PD 60. On PD 65, animals were submitted to a challenge with diethylpropion (DEP), an amphetamine-like drug and different responses were analyzed: locomotor activity, immmunocontent of dopamine related proteins, and the oxidative status in the striatum, before and after the DEP challenge. We showed that a short post-weaning social isolation (SI) increased the locomotor response to DEP, when compared with previous saline administration. Social isolation also increased dopamine transporter, tyrosine hydroxylase, and decreased dopamine D2 receptor immunocontent. Additionally, SI increased the overall oxidative status parameters after the challenge with DEP. Interestingly, the exposure to a HSD prevented the SI effects on locomotor response, but did not interfere in the dopaminergic parameters evaluated, despite having modified some oxidative parameters. This study showed for the first time that a short post-weaning social isolation was able to induce long-term changes in the striatal dopaminergic system and increased the response to psychostimulants. These results emphasize the importance of stressful experiences during a short period of development on programming susceptibility to psychostimulants later in life.
Abstract This study examined the effects of two chronic stress regimens upon depressive-like behavior, A1 and A2A adenosine receptor binding and immunocontent. Male rats were subjected to ...unpredictable chronic mild stress (UCMS) or to chronic restraint stress (CRS) for 40 days. Subsequently, depressive-like behaviors (forced swimming and consumption of sucrose) were evaluated, and A1 adenosine or A2A adenosine receptors were examined in the hippocampus or striatum, respectively. UCMS animals demonstrated depressive-related behaviors (decrease in sucrose consumption and increased immobility in the forced swimming test). This group also presented increased A1 adenosine receptor binding and immunoreactivity in hippocampus, as well as increased striatal A2A adenosine receptor binding in the striatum, without alteration in immunoreactivity. Conversely, the chronic restraint stress group displayed only an increase in A1 adenosine receptor binding and no alteration in the other parameters evaluated. We suggest that the alteration in adenosine receptors, particularly the upregulation of striatal A2A adenosine receptors following UCMS, could be associated with depressive-related behavior.
PDF
