Effects of a Functional Food Made with Salvia hispanica L. (Chia Seed), Amaranthus hypochondriacus L. (Amaranth), and an Ethanolic Extract of Curcuma longa L. (Curcumin) in a Rat Model of Childhood Obesity.

Obesity is a global health problem and is increasing in prevalence in most countries. Although obesity affects all age groups, children are the most vulnerable sector. Functional foods are novel formulated foods containing substances (i.e., nutrients, phytochemicals, probiotics, etc.) that have potential health-enhancing or disease-preventing value. The research objective was to study the possible beneficial effects of providing a functional food made with amaranth flour, chia seed, and curcumin extract on the metabolism and behavior of a rat model of childhood obesity. Male Wistar rat pups from two litters of different sizes, a normal litter (NL) (10 pups) and a small litter (SL) (4 pups), were used. After weaning, the rats were fed a hypercaloric diet (HD) or an HD supplemented with the functional food mixture. Body weight and energy intake were measured for seven weeks, and locomotor activity, learning, and memory tests were also performed. At the end of the experiment, glucose and lipid metabolism parameters were determined. The results showed that in this model of obesity produced by early overfeeding and the consumption of a hypercaloric diet, anxiety-like behaviors and metabolic alterations occurred in the rat offspring; however, the provision of the functional food failed to reduce or prevent these alterations, and an exacerbation was even observed in some metabolic indicators. Interestingly, in the NL rats, the provision of the functional food produced some of the expected improvements in health, such as significant decreases in body weight gain and liver cholesterol and non-significant decreases in adipose tissue and leptin and insulin serum levels.

Structure, Absolute Configuration, Antiproliferative and Phytotoxic Activities of Icetexane and Abietane Diterpenoids from Salvia carranzae and Chemotaxonomic Implications.

From the aerial parts of Salvia carranzae Zamudio and Bedolla, three new icetexane-type diterpenoids were isolated. Their structures were established through spectroscopic methods and named the following: salvicarranzanolide (1), 19-deoxo-salvicarranzanolide (2) and 19-deoxo-20-deoxy-salvicarranzanolide (3). In addition, the known icetexane-type diterpenoids, 6,7,11,14-tetrahydro-7-oxo-icetexone (4), iso-icetexone (5), 19-deoxo-iso-icetexone (6), icetexone (7), 19-deoxo-icetexone (8) and 7α-acetoxy-6,7-dihydroicetexone (9), were also isolated, along with the abietanes sessein (10) and ferruginol (11). α-Tocopherol was also identified. Compounds 5, 6 and 8 were tested for their antiproliferative activity using the sulforhodamine B assay on six cancer and one normal human cell lines. Diterpenoids 5 and 6 showed noteworthy antiproliferative activity, exhibiting an IC50 (µM) = 0.43 ± 0.01 and 1.34 ± 0.04, respectively, for U251 (glioblastoma), an IC50 (µM) = 0.45 ± 0.01 and 1.29 ± 0.06 for K5621 (myelogenous leukemia), 0.84 ± 0.07 and 1.03 ± 0.10 for HCT-15 (colon cancer), and 0.73 ± 0.06 and 0.95 ± 0.09 for SKLU-1 (lung adenocarcinoma) cell lines. On the other hand, the phytotoxicity of compounds 5-7 and 9-10 was evaluated on seed germination and root growth in some weeds such as Medicago sativa, Panicum miliaceum, Amaranthus hypochondriacus and Trifolium pratense as models. While compounds 5 and 10 exhibited a moderate inhibitory effect on the root growth of A. hypochondriacus and T. pratense at 100 ppm, the diterpenoids 6, 7 and 9 were ineffective in all the plant models. Taxonomic positions based on the chemical profiles found are also discussed.

Changes in the Dentate Gyrus Gene Expression Profile Induced by Levetiracetam Treatment in Rats with Mesial Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT-qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT-qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1, Adam8, Slc24a1, and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca2+ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients.

Thalidomide Attenuates Epileptogenesis and Seizures by Decreasing Brain Inflammation in Lithium Pilocarpine Rat Model.

Thalidomide (TAL) has shown potential therapeutic effects in neurological diseases like epilepsy. Both clinical and preclinical studies show that TAL may act as an antiepileptic drug and as a possible treatment against disease development. However, the evidence for these effects is limited. Therefore, the antiepileptogenic and anti-inflammatory effects of TAL were evaluated herein. Sprague Dawley male rats were randomly allocated to one of five groups (n = 18 per group): control (C); status epilepticus (SE); SE-TAL (25 mg/kg); SE-TAL (50 mg/kg); and SE-topiramate (TOP; 60mg/kg). The lithium-pilocarpine model was used, and one day after SE induction the rats received pharmacological treatment for one week. The brain was obtained, and the hippocampus was micro-dissected 8, 18, and 28 days after SE. TNF-α, IL-6, and IL-1ß concentrations were quantified. TOP and TAL (50 mg/kg) increased the latency to the first of many spontaneous recurrent seizures (SRS) and decreased SRS frequency, as well as decreasing TNF-α and IL-1ß concentrations in the hippocampus. In conclusion, the results showed that both TAL (50 mg/kg) and TOP have anti-ictogenic and antiepileptogenic effects, possibly by decreasing neuroinflammation.

Neonatal ventral hippocampus lesion disrupts maternal behavior in rats: An animal model of schizophrenia.

Although individuals with schizophrenia typically present deficits in social interaction, little is known about the quality of their parent-infant interactions. In the present study, we assessed the behavioral effects of neonatal ventral hippocampus lesion (nVHL) in female rats (nVHL is known to induce schizophrenia-like deficits in males). Sexually naïve adult nVHL or sham female rats received cognitive and social tests, and their maternal behavior was observed in independent groups of adult nVHL and sham rats on postpartum days 2, 6, and 12. Compared to Sham females, naïve nVHL rats displayed elevated locomotor activity, less social interaction, and disrupted habituation of the acoustic startle response (ASR), while dorsal immobility (a defensive behavioral response) and prepulse inhibition of ASR were not affected. Although all nVHL mothers retrieved their pups, adopted the crouching posture, and nursed them, they showed disturbances in the display of pup body licking and nest building. Furthermore, a high proportion of nVHL mothers displayed atypical retrieval of pups and re-retrieving of pups, atypical nest-building, excavation, and cannibalism, as well a high level of these behaviors. These data indicate that cognition, locomotor activity, and maternal care is disrupted in nVHL female, suggesting disturbances in mesocorticolimbic dopaminergic systems and/or in social cognition.

Levetiracetam Mechanisms of Action: From Molecules to Systems.

Epilepsy is a chronic disease that affects millions of people worldwide. Antiepileptic drugs (AEDs) are used to control seizures. Even though parts of their mechanisms of action are known, there are still components that need to be studied. Therefore, the search for novel drugs, new molecular targets, and a better understanding of the mechanisms of action of existing drugs is still crucial. Levetiracetam (LEV) is an AED that has been shown to be effective in seizure control and is well-tolerable, with a novel mechanism of action through an interaction with the synaptic vesicle protein 2A (SV2A). Moreover, LEV has other molecular targets that involve calcium homeostasis, the GABAergic system, and AMPA receptors among others, that might be integrated into a single mechanism of action that could explain the antiepileptogenic, anti-inflammatory, neuroprotective, and antioxidant properties of LEV. This puts it as a possible multitarget drug with clinical applications other than for epilepsy. According to the above, the objective of this work was to carry out a comprehensive and integrative review of LEV in relation to its clinical uses, structural properties, therapeutical targets, and different molecular, genetic, and systemic action mechanisms in order to consider LEV as a candidate for drug repurposing.

Antidepressant-like effects of acupuncture via modulation of corticosterone, sex hormones, and hippocampal BDNF expression in male rats.

BACKGROUND: Post-weaning social isolated rodents exhibit pathophysiological changes associated with depression including adrenal axis hyperactivity, gonadal hormone level disturbances, molecular alterations in hippocampus, and immobility behavior in the forced swimming test (FST). Although acupuncture by absorbable thread implantation (acu-catgut, AC) elicits antidepressant-like effects in social isolated rats, AC effects on neuroendocrine and hippocampal molecular alterations have been less characterized. OBJECTIVE: To investigate the participation of gonadal hormones, corticosterone, and brain-derived neurotrophic factor (BDNF) hippocampal expression, on the AC antidepressant-like effects in social isolated male rats. METHODS: Sprague-Dawley male rats were raised in social isolation (SI) or standard conditions, for 11 weeks. AC (on Baihui (Du20), Yintang (E X-HN3), Shenshu (BL 23), Pishu (BL 20), Ganshu (BL 18), Xinshu (BL 15) and Guanyuan (Ren 4)), or Sham-AC (puncturing of acupoints without embedding the thread), was applied during the last three weeks of isolation period. Rats were evaluated in the FST; hormones plasmatic levels and hippocampal BDNF content were quantified by ELISA and Western blotting, respectively. RESULTS: Social isolated rats showed more immobility in the FST and had lower testosterone and estradiol levels, higher corticosterone levels, and reduced hippocampal BDNF content than controls. BDNF level in hippocampus inversely correlated to depression-like behavior. AC but not sham-AC normalized immobility behavior, steroid hormone levels, and BDNF content, as in rats raised in a social environment. CONCLUSIONS: AC antidepressant effect could be related to an improvement of hippocampal BDNF protein expression, as well as corticosterone and sex hormones disturbances associated with prolonged exposure to stress caused by social isolation. Present findings have implications for depression treatment in individuals early exposed to stress.

The high-fructose intake of dams during pregnancy and lactation exerts sex-specific effects on adult rat offspring metabolism.

Experimental studies have demonstrated the effects of maternal fructose consumption during pregnancy and lactation on metabolic alterations in their offspring, especially male offspring. However, few studies have focused on female offspring after providing fructose in food to dam rats. Here, we studied whether offspring of both sexes were differentially affected by a maternal high-fructose diet (HFD). For this purpose, Sprague-Dawley rats were fed during pregnancy and lactation with a standard diet (SD) or a HFD (50% w/w). After weaning, offspring were fed an SD; 3 days later, dams were sacrificed, and their offspring were sacrificed on postnatal day 90. Body weight (BW), food and water intake (only for dams), and various biomarkers of metabolic syndrome were measured. When compared to the SD-fed dams, HFD-fed dams had a reduction in BW and food and water intake. Conversely, adiposity, liver weight, liver lipids, and plasma levels of glucose, insulin, cholesterol, triglycerides, and uric acid were increased in HFD-fed dams. Moreover, the BW, food consumption, weight of retroperitoneal fat pads, and liver lipids increased in female and male offspring of HFD-fed dams. Interestingly, the pups of HFD-fed mothers showed increased levels of leptin and insulin resistance and decreased levels of adiponectin which were more pronounced in male offspring than in female offspring. In contrast, a higher increase in BW was shown earlier in female offspring. Thus, high-fructose consumption by dams during pregnancy and lactation led to sex-specific developmental programming of the metabolic syndrome phenotype in adult offspring.

Characterization of the antiapoptotic effect of copper sulfate on striatal and midbrain damage induced by MPP+ in rats.

1-Methyl-4-phenylpyridinium ion (MPP+)-induced neurotoxicity produces cellular damage resembling that encountered in Parkinson's disease. The mechanisms of cellular death after MPP+ include the participation of oxidative stress in the loss of dopaminergic neurons. Among the mechanisms of defense against oxidative stress, several copper-dependent proteins have been implicated: Cu/Zn-SOD, ceruloplasmin, and metallothionein. Another important mechanism of damage, is MPP + interference with mitochondrial respiration. Both, oxidative stress and inhibition of mitochondrial respiration may trigger apoptosis in the neurons after MPP+. The aim of the present study was to characterize the time-course of apoptosis induced by MPP+ to determine if copper sulfate pretreatment is able to prevent the activation of caspases and decreased the neuronal apoptosis. MPP+ was microinjected into rat striatum using a stereotactic frame. The results showed increased activities of caspases 8, 9 and 3, between 72-120 hours after administration of MPP+, both in striatum and midbrain. After this study, we tested the effect of CuSO4 on MPP+ neurotoxicity, showing a diminution of the apoptotic damage induced by MPP+, decreased levels of enzymatic activity of caspases: 8 (-34 and -25 %), 9 (-25 and -42 %) and 3 (-40 and -29 %) in striatum and midbrain, respectively. Finally, we performed an immunohistochemical analysis, evidencing a decreased number of apoptotic cells in the groups pretreated with copper sulfate pretreatment compared to the control group. With these findings, it is concluded that pretreatment with copper sulfate may be a good alternative to prevent MPP+-induced apoptosis.

Levetiracetam Reduced the Basal Excitability of the Dentate Gyrus without Restoring Impaired Synaptic Plasticity in Rats with Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive dysfunction. The long-lasting effect of LEV treatment and its participation in synaptic plasticity have not been explored in early chronic epilepsy. Therefore, through the measurement of evoked field potentials, this study aimed to comprehensively identify the alterations in the excitability and the short-term (depression/facilitation) and long-term synaptic plasticity (long-term potentiation, LTP) of the dentate gyrus of the hippocampus in a lithium-pilocarpine rat model of TLE, as well as their possible restoration by LEV (1 week; 300 mg/kg/day). TLE increased the population spike (PS) amplitude (input/output curve); interestingly, LEV treatment partially reduced this hyperexcitability. Furthermore, TLE augmented synaptic depression, suppressed paired-pulse facilitation, and reduced PS-LTP; however, LEV did not alleviate such alterations. Conversely, the excitatory postsynaptic potential (EPSP)-LTP of TLE rats was comparable to that of control rats and was decreased by LEV. LEV caused a long-lasting attenuation of basal hyperexcitability but did not restore impaired synaptic plasticity in the early chronic phase of TLE.

Neuropharmacological Screening of Chiral and Non-chiral Phthalimide- Containing Compounds in Mice: in vivo and in silico Experiments.

BACKGROUND: Thalidomide, the first synthesized phthalimide, has demonstrated sedative- hypnotic and antiepileptic effects on the central nervous system. N-substituted phthalimides have an interesting chemical structure that confers important biological properties. OBJECTIVE: Non-chiral (ortho and para bis-isoindoline-1,3-dione, phthaloylglycine) and chiral phthalimides (N-substituted with aspartate or glutamate) were synthesized and the sedative, anxiolytic and anticonvulsant effects were tested. METHOD: Homology modeling and molecular docking were employed to predict recognition of the analogues by hNMDA and mGlu receptors. The neuropharmacological activity was tested with the open field test and elevated plus maze (EPM). The compounds were tested in mouse models of acute convulsions induced either by pentylenetetrazol (PTZ; 90 mg/kg) or 4-aminopyridine (4-AP; 10 mg/kg). RESULTS: The ortho and para non-chiral compounds at 562.3 and 316 mg/kg, respectively, decreased locomotor activity. Contrarily, the chiral compounds produced excitatory effects. Increased locomotor activity was found with S-TGLU and R-TGLU at 100, 316 and 562.3 mg/kg, and S-TASP at 316 and 562.3 mg/kg. These molecules showed no activity in the EPM test or PTZ model. In the 4-AP model, however, S-TGLU (237.1, 316 and 421.7 mg/kg) as well as S-TASP and R-TASP (316 mg/kg) lowered the convulsive and death rate. CONCLUSION: The chiral compounds exhibited a non-competitive NMDAR antagonist profile and the non-chiral molecules possessed selective sedative properties. The NMDAR exhibited stereoselectivity for S-TGLU while it is not a preference for the aspartic derivatives. The results appear to be supported by the in silico studies, which evidenced a high affinity of phthalimides for the hNMDAR and mGluR type 1.

Antidepressant effects of acupoint stimulation and fluoxetine by increasing dendritic arborization and spine density in CA1 hippocampal neurons of socially isolated rats.

Given the importance of depression and the adverse effects of conventional treatment, it is necessary to seek complementary therapies. In a rat model of depression, this study aimed to assess the behavioral and morphological effects of embedding absorbable thread in acupoints (acu-catgut), and compare the results to those of fluoxetine treatment and the corresponding control groups. Therefore, depressive-like behavior was evaluated with the forced swimming test, and dendritic morphology (in the CA1 hippocampal region) with the Golgi-Cox technique and Sholl analysis. After weaning, male Sprague-Dawley rats were housed in social isolation for 8 weeks to induce depressive-like behavior. They were then given a 21-day treatment by stimulating acupoints with acu-catgut (AC) or fluoxetine (FX) (2 mg/kg). Rats were divided into six groups: Control (socially housed), social isolation (SI), SI + AC, SI + Sham (sham embedding of thread), SI + FX and SI + VH (vehicle). Compared to fluoxetine, acu-catgut treatment was more effective in reversing depressive-like behavior elicited by SI. The SI-induced reduction in dendritic length and spine density in hippocampal CA1 pyramidal neurons was attenuated after prolonged treatment with acu-catgut or fluoxetine. Hence, both treatments proved capable of reversing depressive-like alterations caused by SI, likely due to dendritic remodeling in the hippocampus.

Neurotensin-polyplex-mediated brain-derived neurotrophic factor gene delivery into nigral dopamine neurons prevents nigrostriatal degeneration in a rat model of early Parkinson's disease.

BACKGROUND: The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) influences nigral dopaminergic neurons via autocrine and paracrine mechanisms. The reduction of BDNF expression in Parkinson's disease substantia nigra (SN) might contribute to the death of dopaminergic neurons because inhibiting BDNF expression in the SN causes parkinsonism in the rat. This study aimed to demonstrate that increasing BDNF expression in dopaminergic neurons of rats with one week of 6-hydroxydopamine lesion recovers from parkinsonism. The plasmids phDAT-BDNF-flag and phDAT-EGFP, coding for enhanced green fluorescent protein, were transfected using neurotensin (NTS)-polyplex, which enables delivery of genes into the dopaminergic neurons via neurotensin-receptor type 1 (NTSR1) internalization. RESULTS: Two weeks after transfections, RT-PCR and immunofluorescence techniques showed that the residual dopaminergic neurons retain NTSR1 expression and susceptibility to be transfected by the NTS-polyplex. phDAT-BDNF-flag transfection did not increase dopaminergic neurons, but caused 7-fold increase in dopamine fibers within the SN and 5-fold increase in innervation and dopamine levels in the striatum. These neurotrophic effects were accompanied by a significant improvement in motor behavior. CONCLUSIONS: NTS-polyplex-mediated BDNF overexpression in dopaminergic neurons has proven to be effective to remit hemiparkinsonism in the rat. This BDNF gene therapy might be helpful in the early stage of Parkinson's disease.

Hypericum silenoides†Juss. and Hypericum philonotis†Cham. & Schlecht. extracts: in-vivo hypolipidaemic and weight-reducing effects in obese rats.

OBJECTIVES: This study was carried out to assess the anti-obesity effect of Hypericum silenoides Juss. and Hypericum philonotis Cham. & Schlecht. in male Wistar rats fed with a cafeteria diet. METHODS: Adult male Wistar rats with an initial body weight of 290-320 g were used in this trial. The rats were fed with a cafeteria diet for 77 days. Hypericum species were administered orally at a dose of 10, 30 or 100 mg/kg of body weight daily for 35 days. Body weight, food intake, anorexic effect and various biochemical parameters, such as serum glucose, lipid profile, alanine transaminase (ALT), aspartate transaminase (AST) and atherogenic index (AI), were assessed. Additionally, inhibitory lipase activity assay and forced swimming test were also carried out. KEY FINDINGS: Oral administration of H. silenoides and H. philonotis extracts resulted in a significant decrease in body weight and serum glucose levels in obese male Wistar rats. Treatment with aqueous extract of H. silenoides showed anorexic and antidepressant effects and also significantly (P < 0.05) decreased total cholesterol, triglycerides and high-density lipoprotein-cholesterol, while low-density lipoprotein-cholesterol, AI, AST and ALT were not changed. The dichloromethane extract of H. silenoides (half maximal inhibitory concentration (IC50 ) = 262.79 ± 0.09 µg/ml) and hexane extract of H. philonotis (IC50 = 162.60 ± 0.02 µg/ml) showed the most potent lipase inhibitory activity. CONCLUSION: Some H. silenoides and H. philonotis extracts showed a significant anti-obesity activity in cafeteria-diet-fed rats. This research provides the first scientific support for the use of the Hypericum genus for weight reduction in Mexican folk medicine.

Corticosterone microinjected into nucleus pontis oralis increases tonic immobility in rats.

Tonic immobility (TI) is also known as "immobility response", "immobility reflex", "animal hypnosis", etc. It is an innate antipredatory behavior characterized by an absence of movement, varying degrees of muscular activity, and a relative unresponsiveness to external stimuli. Experimentally, TI is commonly produced by manually forcing an animal into an inverted position and restraining it in that position until the animal becomes immobile. Part of the neural mechanism(s) of TI involves the medullo-pontine reticular formation, with influence from other components of the brain, notably the limbic system. It has been observed that TI is more prolonged in stressed animals, and systemic injection of corticosterone (CORT) also potentiates this behavior. At present, the anatomical brain regions involved in the CORT modulation of TI are unknown. Thus, our study was made to determine if some pontine areas could be targets for the modulation of TI by CORT. A unilateral nucleus pontis oralis (PnO) microinjection of 1 µL of CORT (0.05 µg/1 µL) in rats resulted in clear behavioral responses. The animals had an increased duration of TI caused by clamping the neck (in this induction, besides of body inversion and restraint, there is also clamping the neck), with an enhancement in open-field motor activity, which were prevented by pretreatment injection into PnO with 1 µL of the mineralocorticoid-receptor antagonist spironolactone (0.5 µg/1 µL) or 1 µL of the glucocorticoid-receptor antagonist mifepristone (0.5 µg/1 µL). In contrast, these behavioral changes were not seen when CORT (0.05 µg/1 µL) was microinjected into medial lemniscus area or paramedian raphe. Our data support the idea that, in stressful situations, glucocorticoids released from adrenals of the prey reach the PnO to produce a hyper arousal state, which in turn can prolong the duration of TI.

Differential Effect of the Dopamine D3 Agonist (±)-7-Hydroxy-2-(N,N-di-n-propylamino) Tetralin (7-OH-DPAT) on Motor Activity between Adult Wistar and Sprague-Dawley Rats after a Neonatal Ventral Hippocampus Lesion.

The neonatal ventral hippocampal lesion (nVHL) has been widely used as an animal model for schizophrenia. Rats with an nVHL show several delayed behavioral alterations that mimic some symptoms of schizophrenia. Sprague-Dawley (SD) rats with an nVHL have a decrease in D3 receptors in limbic areas, but the expression of D3 receptors in Wistar (W) rats with an nVHL is unknown. The 7-Hydroxy-2-(N,N-di-n-propylamino) tetralin (7-OH-DPAT) has been reported as a D3-preferring agonist. Thus, we investigated the effect of (±)-7-OH-DPAT (0.25 mg/kg) on the motor activity in male adult W and SD rats after an nVHL. The 7-OH-DPAT caused a decrease in locomotion of W rats with an nVHL, but it did not change the locomotion of SD rats with this lesion. Our results suggest that the differential effect of 7-OH-DPAT between W and SD rats with an nVHL could be caused by a different expression of the D3 receptors. These results may have implications for modeling interactions of genetic and environmental factors involved in schizophrenia.

The effects of acute stress and acute corticosterone administration on the immobility response in rats.

The immobility response is an innate antipredatory behavior in a broad variety of species. The immobility response varies in its postural components but in general is characterized by an absence of movement and a relative unresponsiveness to stimuli. Experimentally in rats, clamping the neck followed by body inversion and manual restrain elicits a response called "immobility by clamping the neck". Stress reactions protect animals against predators and are characterized by activation of the sympathetic and hypothalamic-pituitary-adrenal systems. However, in mammals, the role of acute stress as a modulator of immobility response has been less studied. The aim of our study was to assess the effects of acute stress and the injection of corticosterone (5mg/kg, ip) on immobility by clamping the neck in rats. We observed that either previous acute stress caused by forced exposure to elevated open platform or application of a heat-pain stimulus to the rat's tail during the immobility increased the duration of the immobility response caused by clamping the neck. Also, the corticosterone produced a rapid increase (15 min after injection) in the duration of this immobility response. Our results show that the acute stress, in rats, is a facilitator of the immobility response and suggest a possible nongenomic rapid action of corticosterone over brain structures that control this behavior.

Immobility response elicited by clamping the neck induces antinociception in a "tonic pain" test in mice.

Clamping the neck followed by body inversion to a supine position in mice elicits an immobility response called immobility by clamping the neck (ICN). The noxious pinch to the scruff of the neck produces antinociception in "phasic pain" models (e.g. tail-flick test). Here, a "tonic pain" model was used to test the antinociception associated with the ICN, and naloxone was used to determine the role of opioids in such antinociception. Mice were injected intraperitoneally with 0.3 mL of 0.4% acetic acid to produce writhing responses that were measured for one hour. ICN was induced every five minutes for one hour. Naloxone (5 mg/kg ip) was injected 10 min before acetic acid administration. There was a control group, sham clamping (SCLA). These mice were handled and restricted every five minutes as in the ICN but without real clamping. The repetitive inductions of ICN were able to reduce the writhing behavior; this antinociception was blocked by the naloxone pretreatment. In the SCLA group antinociception was not observed. These findings indicate that as in the "phasic pain" model, ICN also was able to elicit antinociception in this "tonic pain" model, and such antinociception seems to be mediated by opioids.