Evidence for the contribution of multiple mechanisms in the feeding pattern of rats exposed to p-chloro-diphenyl diselenide-supplemented diets.

Preliminary findings suggest that food intake reduction induced by p-chloro-diphenyl diselenide [(p-ClPhSe)2] in rats is mediated by a satiating action; however, additional experiments are necessary to clarify its actions. The purpose of this study was to investigate the effects of diets supplemented with (p-ClPhSe)2 on feeding behavior of rats as well as the (p-ClPhSe)2 effectiveness in producing aversive reactions or specific flavor. The results demonstrated that behavioral satiety sequence (BSS) was preserved in animals exposed to (p-ClPhSe)2-supplemented diets (0.01 and 0.1%) and associated with a shift of the onset of resting to the left indicating a satiating action at the first contact. In addition, the frequency, the mean duration and the mean size of meals were decreased in rats exposed to a 0.1% (p-ClPhSe)2 diet. Alternatively, a second contact with a 0.01% (p-ClPhSe)2 diet caused disruption of BSS and pronounced changes in the meal pattern, suggesting that it produces aversiveness. In fact, rats developed a significant taste aversion to the saccharin solution after receiving the administration of (p-ClPhSe)2 (1 and 10mg/kg; i.p.). Lastly, a diet containing 0.1% of (p-ClPhSe)2 seems to alter the palatability of food given that rats had a preference for the control diet. The findings of the present study suggest that (p-ClPhSe)2 reduced the food intake of rats by inducing a satiating action at the first contact, but it also produced aversive reactions when rats were re-exposed to it. A specific flavor seems also to contribute to (p-ClPhSe)2 suppressant effects on feeding.

Effects of diphenyl and p-chloro-diphenyl diselenides on feeding behavior of rats.

RATIONALE: The searching for safe and effective antiobesity drugs has been the subject of intense research. Previous studies have shown several pharmacological applications of organoselenium compounds; however, their possible anorectic-like actions have not been investigated. OBJECTIVE: This study aims to investigate the effects of (PhSe)2 and (p-ClPhSe)2 on feeding behavior of rats and their potential as weight-reducing agents. METHODS: The effects of intraperitoneal administration of diselenides were investigated through the microstructural pattern of feeding behavior, behavioral satiety sequence (BSS), hypothalamic serotonin (5-HT) uptake, body weight, and epididymal fat content of male rats. RESULTS: Our findings demonstrated that food intake of fasted rats was reduced by both diselenides (1 and 10 mg/kg). Diphenyl diselenide [(PhSe)2] (1 mg/kg) and p-chloro-diphenyl diselenide [(p-ClPhSe)2] (10 mg/kg) decreased the frequency, mean duration, and mean size of meals compared with the control treatment. The BSS structure was preserved when organoselenium compounds (1 mg/kg) were administered, and it was associated to a displacement to the left when the resting period started indicating a satiating action. Inhibition of 5-HT uptake in the hypothalamus (∼20 %) was also found in rats treated with low doses of (PhSe)2 and (p-ClPhSe)2 (1 mg/kg). Treatments with a high dose of both diselenides (10 mg/kg) carried out for 7 days induced weight loss and epididymal fat reduction in sated rats. CONCLUSION: This study suggests that diselenides caused a satiating action in rats that could be partially explained by the inhibition of hypothalamic 5-HT uptake. These organoselenium compounds were potential weight-reducing agents when repeatedly administered.

Caffeine suppresses exercise-enhanced long-term and location memory in middle-aged rats: Involvement of hippocampal Akt and CREB signaling.

The cognitive function decline is closely related with brain changes generated by age. The ability of caffeine and exercise to prevent memory impairment has been reported in animal models and humans. The purpose of the present study was to investigate whether swimming exercise and caffeine administration enhance memory in middle-aged Wistar rats. Male Wistar rats (18months) received caffeine at a dose of 30mg/kg, 5days per week by a period of 4weeks. Animals were subjected to swimming training with a workload (3% of body weight, 20min per day for 4weeks). After 4weeks, the object recognition test (ORT) and the object location test (OLT) were performed. The results of this study demonstrated that caffeine suppressed exercise-enhanced long-term (ORT) and spatial (OLT) memory in middle-aged and this effect may be related to a decrease in hippocampal p-CREB signaling. This study also provided evidence that the effects of this protocol on memory were not accompanied by alterations in the levels of activated Akt. The [(3)H] glutamate uptake was reduced in hippocampus of rats administered with caffeine and submitted to swimming protocol.

Monosodium glutamate, a food additive, induces depressive-like and anxiogenic-like behaviors in young rats.

UNLABELLED: Monosodium glutamate (MSG) has been the target of research due to its toxicological effects. AIMS: We investigated the depressive- and anxiogenic-like behaviors in rats exposed to neonatal subcutaneous injection of MSG. The involvement of the serotonergic system, by measuring [(3)H] serotonin (5-HT) uptake in cerebral cortices, and the hypothalamic pituitary adrenal (HPA) axis, by determining serum adrenocorticotropic hormone (ACTH) and corticosterone levels, was also examined. MATERIALS AND METHODS: Male and female newborn Wistar rats were divided into control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4 g/kg/day) from the 1st to 5th postnatal day. The behavioral tests [spontaneous locomotor activity, contextual fear conditioning, and forced swimming test (FST)] were performed from the 60th to 64th postnatal day. MSG-treated animals showed alteration in the spontaneous locomotor activity, an increase in the number of fecal pellets and the number of animal's vocalizations and urine occurrence, and a decrease in the grooming time. KEY FINDINGS: The MSG exposure increased the immobility time in the FST and the freezing reaction in the contextual fear conditioning. Additionally, MSG treatment increased the [(3)H]5-HT uptake in the cerebral cortices of rats and induced a deregulation of HPA axis function (by increasing serum ACTH and corticosterone levels). SIGNIFICANCE: In conclusion MSG-treated rats are more susceptible to develop anxiogenic- and depressive-like behaviors, which could be related to a dysfunction in the serotonergic system.

Trypanosoma evansi infection impairs memory, increases anxiety behaviour and alters neurochemical parameters in rats.

The aim of this study was to investigate neurochemical and enzymatic changes in rats infected with Trypanosoma evansi, and their interference in the cognitive parameters. Behavioural assessment (assessment of cognitive performance), evaluation of cerebral L-[3H]glutamate uptake, acetylcholinesterase (AChE) activity and Ca+2 and Na+, K+-ATPase activity were evaluated at 5 and 30 days post infection (dpi). This study demonstrates a cognitive impairment in rats infected with T. evansi. At 5 dpi memory deficit was demonstrated by an inhibitory avoidance test. With the chronicity of the disease (30 dpi) animals showed anxiety symptoms. It is possible the inhibition of cerebral Na+, K+-ATPase activity, AChE and synaptosomal glutamate uptake are involved in cognitive impairment in infected rats by T. evansi. The understanding of cerebral host­parasite relationship may shed some light on the cryptic symptoms of animals and possibly human infection where patients often present with other central nervous system (CNS) disorders.

Ebselen reduces hyperglycemia temporarily-induced by diazinon: a compound with insulin-mimetic properties.

The present study investigated the effect of ebselen (EB) against hyperglycemia induced by the organophosphate (OPI) diazinon (DI) in rats. The insulin-mimetic properties of EB were investigated in vitro with the aim of better understanding the hypoglycemic effect of this compound. The protective effect of EB against pancreatic and hepatic damage caused by DI in rats was also appraised. In the in vivo experiments, rats were pre-treated with a single injection of EB (50mg/kg, intraperitoneal, i.p.). Afterward, animals were treated with a single injection of DI (200 mg/kg, i.p.). The parameters indicative of pancreatic and hepatic damage such as, serum amylase, lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities as well as serum glucose levels, hepatic glycogen content and glucose-6-phosphatase (G6Pase) activity were determined. EB pre-treatment was effective in reducing serum amylase, lipase, AST, ALT, ALP, and LDH activities, protecting against pancreatic and hepatic damage. EB reduced hyperglycemia and increased hepatic glycogen content in animals exposed to DI. In the in vitro assays, EB (150 µM) or insulin (IN 10 µM, positive control) was incubated with either skeletal muscle or hepatic tissue with the aim of measuring glucose uptake, glycogen synthesis and glycogen breakdown. EB increased the glucose uptake in skeletal muscle, stimulated hepatic glycogen synthesis and inhibited glycogen breakdown in a similar way to IN. In conclusion, EB, possibly through its insulin-mimetic action, protected against pancreatic and hepatic damage caused by DI in rats.

Synthesis and antidepressant-like activity of selenophenes obtained via iron(III)-PhSeSePh-mediated cyclization of Z-selenoenynes.

We present here the synthesis and antidepressant-like action of a series of 2,5-disubstituted-3-(organoseleno)-selenophenes prepared by a novel synthetic route, the FeCl(3)-diorganyl dichalcogenide-mediated intramolecular cyclization of (Z)-chalcogenoenynes. The cyclized products were obtained in good yields. The results showed that 2c, 2d, 2e and 2o, evaluated in the mouse forced-swimming test, elicited an antidepressant-like activity. The studies clearly show that the phenyl group at the 2-position and an organoselenium group at the 3-position of the selenophene ring are essential for the antidepressant-like activity of selenophenes. A close inspection of the results also revealed that the fluorophenyl portion in the organoselenium group is fundamental for the antidepressant-like action of this class of organochalcogens.