Effect of prior experience of an environment on scopolamine-induced changes in activity

Rats were given 0 or 30 min prior experience of a 36 in. × 36 in. open field then injected with saline or 0.25 or 4.0 mg/kg scopolamine before being tested in the field for 15 min. With no prior experience both doses of scopolamine produced equivalent increases in ambulation and 4.0 mg/kg increased rearing but neither dose affected grooming; however, with experience scopolamine increased ambulation and rearing in a dose-related way and produced equivalent increases in grooming. The resulting level of ambulation and rearing produced by 4.0 mg/kg was, however, higher and that of 0.25 mg/kg lower (for ambulation) in the experience condition compared to that in the no experience condition. These effects could partly be attributed to a decreased level of each response in the undrugged animals in the experience condition. It was concluded that prior experience of an environment does change scopolamine-induced effects on activity.     

Psychomotor and rewarding properties of the neurosteroids dehydroepiandrosterone sulphate and androsterone: effects on monoamine and steroid metabolism

The neurosteroids, dehydroepiandrosterone sulfate (DHEAS) and androsterone, are implicated in drug addictions. We examined their influence on locomotor activity and reward in male Wistar rats, and on steroid and monoamine metabolism in the hippocampus and striatum. In the open field test, DHEAS injections (10, 40, 80 mg/kg, i.p.) 30 min prior the test had no significant effect on ambulation, but androsterone (10 mg/kg) increased general locomotion and at doses 1-10 mg/kg, increased central field activity, suggestive of an anxiolytic action. In the conditioned place preference test, both steroids had a biphasic effect: DHEAS was rewarding at doses of 10 and 40 mg/kg, but not at 80 mg/kg, while androsterone was rewarding at doses of 1 and 10 mg/kg, but aversive at 40 mg/kg. Monoamine and steroid concentrations were analyzed in homogenates from the hippocampus and striatum of DHEAS and androsterone injected rats. DHEAS reduced the hippocampal dopamine level, increased striatal homovanilic acid (HVA) and decreased the striatal serotonin concentrations. Androsterone did not affect dopamine levels or turnover, but increased noradrenaline concentration and serotonin turnover in the hippocampus. DHEAS administration augmented concentrations of DHEA, pregnenolone, androstendiol and androstentriol in both brain structures, while androsterone injections increased brain levels of androsterone, epiandrosterone, 5α-dihydrotestosterone, and androstandiol. Present data document that although psychobehavioral and neurochemical effects of DHEAS and androsterone differ in several aspects; both neurosteroids have rewarding properties at certain dose ranges, suggesting their likely involvement in addictions, which entail different mechanisms.     

Effect of 5-thio-D-glucose on food and water intakes and on the acquisition and performance of maze tasks in the rat

A potent inhibitor of D-glucose transport across the membrane, 5-thio-D-glucose (5-TDG) was examined with respect to its effect on runway and maze performance as well as on food and water intakes and body weight. In an initial experiemnt, three groups of Sprague-Dawley rats were matched in terms of their performance to learn a runway taks with Noyes pellets serving as the reinforcement. After extinction, two groups of rats were given 5-TDG in their food for 14 days, in doses of 20 and 100 mg/kg/day, which exerts potent effects on other functions. Retesting in the runway task showed no significant differences in the time required for the controls and for the 5-TDG treated rats to reach the goal box. Nonfed controls and the same two groups were again fed 500 ant 100 mg/kg/day 5-TDG and were tested on the 12 problems of the Hebb-Williams maze. Again, no significant differences were found in the number of erros made on the 12 problems by the 5-TDG treated animals or by the controls. Thus, this sugar analogue, administered in doses that affect spermatogenesis and other processes, has no effect on the ability of the rats to perform these tasks. Similarly, the intakes of food and water were unaffected by the systemic administration of 5-TDG.     

Progesterone can either increase or decrease weight gain and adiposity in ovariectomized Syrian hamsters

We examined the effects of estradiol and progesterone on weight gain, food intake, and carcass composition in Syrian hamsters (Mesocricetus auratus). In ovariectomized (OVX) hamsters injections of 5 micrograms/day estradiol benzoate (EB) alone decreased weight gain and adiposity, whereas treatment with progesterone alone (1 or 5 mg/day) resulted in increased weight gain and adiposity. However, concurrent treatment with progesterone and EB reduced body fat content to levels significantly below those of hamsters treated with EB alone. In a second experiment, 17 beta-estradiol and progesterone were administered via subcutaneous Silastic capsules in doses which produce physiological levels of steroids. Implants of estradiol significantly decreased body weight gain and fat content. As in the first experiment, these effects of estradiol were exaggerated by concurrent progesterone administration. Implants of progesterone alone did not affect body weight or fatness in OVX hamsters. These data indicate that estradiol and progesterone interact to decrease body lipid stores in hamsters, whereas in rats progesterone reverses the adiposity-reducing actions of estradiol. This species difference in responses to progesterone could help to explain why rats increase, whereas hamsters decrease, their body lipid stores during pregnancy, when circulating progesterone levels are elevated.     

Impairment of emotional behavior and spatial learning in adult Wistar rats by ferrous sulfate

The aim of this study was to investigate the effects of FeSO₄ on the behavior of adult Wistar rats. Rats were treated with moderate doses of iron (1.5 or 3.0 mg/kg) for 5 consecutive days, and the effects of iron supplementation on emotional behavior were studied. One group of rats was tested in elevated plus-maze and in open field, and other group was tested for learning abilities in water maze and for motor skills in rotarod task. Iron level in the brain was measured in the frontal cortex, cerebellum, basal ganglia and hippocampus. The effects of the iron treatment (in particular, a dose of 3.0 mg/kg) on emotional behavior in the elevated plus maze and in the open field were significant. The effects of iron on spatial learning were less pronounced, but significant impairments due to the treatment were observed during the probe test. Motor skills and procedural learning in the rotarod task were not significantly affected by the treatment. These behavioral impairments were associated with significant iron accumulations in the hippocampus and basal ganglia of rats treated with 3.0 mg/kg iron and are discussed in terms of possible neuronal impairments of these structures. Thus, FeSO₄ administration at 3.0 mg/kg for 5 consecutive days in adult rats overcomes the mechanisms that shield the brain from iron intoxication and leads to behavioral impairments, in particular with respect to emotional behavior.     

Postnatal naltrindole treatments induce behavioural modifications in preweanling rats

To investigate the physiological role of the delta-opioid receptor during the preweanling period, we have studied the effects of chronic (daily injections from birth to postnatal day 19) and acute treatments with the selective delta-antagonist naltrindole (1 mg/kg), on behavioural and nociceptive responses in 20-day old male rats. Behavioural testing was performed using an open field paradigm. Acute naltrindole induced significant decreases in external and total ambulation (horizontal activity) and rearing behaviour (vertical activity), as well as a significant increase in grooming frequency. In animals chronically treated with naltrindole there was an increase in total ambulation one day after the discontinuation of the treatment. In a test of nociception (tail immersion) no significant effect of chronic naltrindole treatment on baseline latencies or of acute naltrindole on latency quotients (post-treatment latency/pre-treatment latency) were found. However, chronic naltrindole administration significantly decreased the latency quotients. The results show that the delta-opioid receptor participates in the tonic regulation of motor activity during the preweanling period and might be involved in certain aspects of stress responsiveness.     

Effects of Chronic Administration of Buspirone to Female Mice in Conditions of Prolonged Psychoemotional Stress

The effects of chronic administration (30?days) of the partial 5-HT_1A receptor agonist buspirone (0.05, 1, and 10?mg/kg?i.p.) on the behavior of female C57BL/6?J mice in conditions of prolonged psychoemotional stress were studied. Stress was produced by keeping females in a cage with an aggressive male on the other side of a perforated partition, along with the daily occurrence of 10-min intermale confrontations between the aggressor and another male placed with it. Chronic administration of buspirone at all the doses tested had no effect on the behavior of the females assessed in the partition and open field tests at the end of the treatment period. The elevated plus maze test showed that buspirone had anxiolytic effects, but only at a dose of 1?mg/kg. In the Porsolt test, buspirone (1?mg/kg) produced a minor increase in the duration of immobility, pointing to some antidepressant effect. Thus, chronic administration of buspirone to females in conditions of prolonged psychoemotional stress had different effects on their behavior depending on the dose and test conditions.     

Differential involvement of cholinergic mechanisms in activity and sociability in rats

Four groups of six rats, injected with saline, 0.1, 0.25 or 1.0 mg/kg scopolamine, were tested in a 36 × 36 in. open field for 10 min. Scopolamine differentially affected ambulation, rearing, social contacts and the social and perimeter distances between rats; and increased corner preference. This experiment shows that several component responses of activity and sociability need to be recorded if a better understanding of the involvement of cholinergic mechanisms in behaviour is to be obtained.     

Morphologic changes induced by oral long-term treatment with 8-prenylnaringenin in the uterus, vagina, and mammary gland of castrated rats

OBJECTIVE: The flavonoid 8-prenylnaringenin (8-PN) is found in hops, and hence in beer, and is also increasingly consumed as a food supplement. It is the strongest known phytoestrogen, which makes it a good candidate as an alternative to hormone therapy. Its putatively undesired estrogenic effects in the uterus and mammary gland have not yet been thoroughly investigated. Therefore, we performed a long-term oral administration experiment. DESIGN: Rats were ovariectomized and fed for 3 months with soy-free chow containing estradiol (E(2)) or 8-PN, both in two doses (8-PN: 6.77 mg or 68.42 mg/kg body weight; E(2): 0.17 mg or 0.7 mg/kg body weight) or no additives. Analysis was mainly focused on morphologic and immunocytochemical parameters. Expression of proliferating cell nuclear antigen as a proliferation marker and of progesterone receptor was quantified in the mammary gland. RESULTS: Uteri of animals treated with both E(2) doses and the high 8-PN dose had increased weight and showed histologic estrogen-induced features. 8-PN at the high dose induced epithelial polypoid formation unique to this group. Compared to the atrophic controls, both E(2) doses and the high 8-PN dose induced hyperplastic epithelia in the vagina. The high doses of E(2) and 8-PN caused secretion in the mammary gland, whereas proliferation and progesterone receptor expression were stimulated by both E(2) doses and the high 8-PN dose. CONCLUSIONS: E(2) and 8-PN share many effects in the three studied organs, but some differences in the mechanism of action appear to exist.     

Effects of ethanol in an open field apparatus: modification by U50488H and WIN 44441-3

The effects of U50488H, a kappa agonist, and WIN 44441-3, a kappa antagonist, and their modification of the effects of ethanol, on the behavior of rats in a modified open field apparatus, was examined. Crossover activity was increased by U50488H. Headpoke activity was decreased by WIN 44441-3 and increased by U50488H. Rearing activity was increased by WIN 44441-3 but was not affected by U50488H. The effect of both drugs was dose related, with the largest doses having no effect. Ethanol (0.5 g/kg) stimulated crossover activity while it depressed rearing, headpoke and corner activities; except for crossover activity the 2.0 g/kg dose of ethanol depressed these activities. Pretreatment with WIN 44441-3 (0.5 mg/kg) potentiated the stimulant effect of ethanol on crossover activity and partially reversed the depressant effect of ethanol on rearing and headpoke activities. U50488H potentiated the ethanol-induced depression of headpoke and reversed the depression of corner activity. Pretreatment with U50488H had no effect on ethanol's action on crossover and rearing behaviors. Our results indicate that kappa opiate receptors may mediate some behaviors exhibited by rats in a modified open field apparatus. Activation of these receptors increases locomotor and headpoke activity but had no effect on rearing activity. Furthermore, the 0.5 g/kg dose of ethanol has differential effects on different measures of open field behavior, while the 2.0 g/kg dose was largely depressant. Our data suggest that some of these effects of ethanol may be mediated via kappa opioid receptors.     

Randomized pilot trial of a synbiotic dietary supplement in chronic HIV-1 infection

Background

Previously, we examined the antidepressant effects of Nelumbinis Semen (NS). In this study, we assessed the anti-depressant effects of NS in the forced swimming test and chronic mild stress (CMS) models of depression and its oral toxicity in rats and dogs.

Methods

In the forced swimming test, NS was intraperitoneally injected before 24?h, 5?h and 1?h of forced swimming test. And the rats were forced to swim for 5?min, the duration of immobility was observed. In CMS models, animals were exposed to a variety of CMS for 8?weeks in order to induce depression-like symptoms. They were treated with NS for the last four weeks of the 8-week CMS and then an open field test was conducted. The anti-depression effects were evaluated based on a measured index, which consisted of visiting counts, start latency, rearing number and grooming time. In the toxicological studies, NS was administered to rats by gavages for 13?weeks at doses of 0, 500, 1000, and 2000?mg/kg/day. To assess the toxicity of NS in beagle dogs, NS was administered orally for 28?days at doses of 0, 500, 1000, 2000 and 4000?mg/kg/day.

Results

400?mg/kg of NS had the lowest immobility times in forced swimming test. And NS significantly reversed the decreased visiting counts, rearing number and grooming time caused by CMS. In addition, NS treatment significantly decreased the start latency. No treatment-related toxicity was detected during 13?weeks administration in rats and 28?days administration in dogs.

Conclusions

Based on the results of this study and previous reports that have examined the anti-depressive effects of NS, NS holds great promise for use in the treatment of depression without causing any adverse effects or toxicities.     

Androgen inhibition of sexual receptivity is modulated by estrogen

Sexual receptivity induced in ovariectomized rats by the long-term administration of estradiol benzoate (EB) can be inhibited by concurrent administration of androgens. Experiment 1 examined the role of time course and dose of androgens in the inhibition of estrogen-induced sexual receptivity. Ovariectomized rats were treated with EB (2.0 microg per rat per day) for 6 days and tested for sexual receptivity (Test Day I). EB treatment continued for 15 days concomitant with daily administration of one of three doses of dihydrotestosterone propionate (DHTP; 7.5, 0.75, 0.075 mg/kg) or 3α-androstanediol (3α-Adiol; 3.75, 1.0, 0.375 mg/kg). Four tests for sexual receptivity were conducted on days 3, 6, 14, and 15 of the androgen/vehicle treatment period (Test Days II-V). On Day 15 (Test Day V), the rats received progesterone (1.0 mg per rat) 4 h before testing. Using the same experimental design, Experiment 2 examined the effect of increasing the dose of estrogen on the androgenic inhibition of sexual receptivity. Ovariectomized rats were treated with one of two doses of EB (2.0 or 10.0 microg per rat per day) concomitant with daily administration of DHTP (7.5 mg/kg) or 3α-Adiol (3.75 mg/kg). In Experiment 1, the highest doses of both DHTP and 3α-Adiol significantly inhibited estrogen-induced sexual receptivity. Data from Experiment 2 indicate that the inhibitory effects of DHTP but not 3α-Adiol can be moderated by an increased dose of EB.     

Depression of rat feeding in familiar and novel environment by sulfated and nonsulfated cholecystokinin octapeptide

The effects of cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated cholecystokinin octapeptide (CCK-8-NS) were tested on feeding by rats in familiar and novel environment. In a familiar environment only intraperitoneally (IP) administered CCK-8-SE (0.8-24 nmole/kg) could inhibit 30 min food intake of 24 hr food-deprived rats, while the same doses of CCK-8-NS IP and both octapeptides (0.8-8000 pmole/rat) intracerebroventricularly (ICV) were totally ineffective. The effects of CCK-8-SE and CCK-8-NS on feeding were also tested in a novel environment, i.e., in an open field. The parameters of exploratory activity and food intake of 24-hr food-deprived rats were recorded simultaneously during a 15-min session. After IP injection, CCK-8-SE dose-dependently depressed the food intake, and the higher doses (8.0 or 24 nmole/kg) also decreased the open field parameters, including number of approaches to food. In the novel environment, 8.0 or 24 nmole/kg IP injected CCK-8-NS also depressed the food intake, whereas the incidence of grooming was enhanced after 8.0 nmole/kg CCK-8-NS. The most effective doses of both octapeptides increased the latency to first bite. For the open field test ICV treatment was also carried out with 8, 80 or 800 pmole doses of the octapeptides, and after 80 pmole CCK-8-SE ICV the food intake was decreased, and after 80 or 800 pmole CCK-8-SE and 800 pmole CCK-8-NS the food intake/approach parameter was depressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of Genotoxicity and Reproductive Toxicity of Silicon Nanocrystals

Silicon crystal 2-5 nm nanoparticles in the form of 1-5-μ granules in water suspension were injected intraperitoneally in a single dose to male F(1)(CBA×C57Bl/6) mice or to outbred albino rats on days 1, 7, and 14 of gestation. Silicon crystal nanoparticles in doses of 5, 25, and 50 mg/kg exhibited no cytogenetic activity in mouse bone marrow cells after 24-h exposure and in doses of 5 and 25 mg/kg after 7 and 14-day exposure. A 24-h exposure to silicon nanoparticles in a dose of 5 mg/kg significantly increased DNA damage (detected by DNA comet assay) in bone marrow cells. In a dose of 50 mg/kg they considerably increased DNA damage in bone marrow and brain cells after exposure of the same duration. Silicon nanoparticles in doses of 5 and 50 mg/kg caused no genotoxic effects in the same cells after 3-h and in a dose of 5 mg/kg after 7-day exposure. Silicon crystal nanoparticles in a dose of 50 mg/kg caused death of 60-80% mice after exposure <24 h. Injected in a dose of 50 mg/kg on days 1, 7, and 14 of gestation, silicon crystal nanoparticles reduced body weight gain in pregnant rats and newborn rats at different stages of the experiment, but had no effect on other parameters of physical development of rat progeny and caused no teratogenic effects.     

Potential teratogenicity of di-n-butyltin dichloride and other dibutyltin compounds.

The developmental toxicity of di-n-butyltin dichloride (DBT-dC) was evaluated in Wistar rats following oral administration. No maternal toxicity, embryotoxicity, or malformations were observed at 1, 2.5, or 5 mg DBT-dC/kg body weight. Signs of maternal toxicity, including decreased food consumption, body weight gain, and thymus weight, were observed at 10 mg/kg body weight DBT-dC. At this dose, no evidence of embryotoxicity, including such measures as total resorptions, viable fetuses, or fetal weights, was noted in any litter data. There was a slightly increased frequency of total malformations at the 10 mg/kg dose level of 4/262 treated vs. 1/269 control fetuses. All defects occurred singly with no clustering nor organ system pattern of occurrence, which would be indicative of a teratogenic effect. The no-observed-adverse-effect-level (NOAEL) for prenatal as well as maternal toxicity was considered to be 5 mg DBT-dC/kg body weight. The interpretation and utility of previously published studies on the developmental toxicity of dibutyltin compounds are confounded by dose regimen and data reporting deficiencies. These studies suggest that, after oral administration during days 6-17 of pregnancy, the NOAEL for malformations in rats of different strains ranges from 1.7 to 5 mg/kg body weight. In these studies, the maternal LD50 was reported to be about 8 mg/kg body weight in one study but at greater than 15 mg/kg in others. Thus, the NOAEL for teratogenicity may be roughly estimated to be from one-tenth to one-third of the maternal LD50. When evaluated, thymus involution, a typical but reversible effect of di- and tri-butyltin compounds, was also observed at 5-10 mg/kg body weight. The most susceptible time for inducing teratogenic effects is reported to be days 7-9 of pregnancy, but malformations have also been found with dosing over longer duration at lower doses. It is doubtful that the findings of malformations at highly toxic doses in animals has any health hazard significance, especially when human exposure to dibutyltins typically occurs at several orders of magnitude lower than the doses used in these studies. Further comparative pharmacokinetic studies would be necessary in order to refine the hazard characterization.     

Behavioral effects of centrally administered LH-RH agonist in rats.

The neuropharmacological actions of the agonist analog D-Trp-6-LH-RH were investigated in several tests after intracerebroventricular (ICV) administrations to male rats. The doses applied were 10, 100 and 1000 ng/animal. In the open field the 1000 ng ICV dose of the peptide D-Trp-6-LH-RH suppressed the ambulation, rearing and grooming. In a combined catalepsy test, the 10 ng and 1000 ng dose of D-Trp-6-LH-RH increased the total duration of immobility. The LH-RH agonist inhibited stereotyped behavior induced by both apomorphine and amphetamine, and the effects of 100 and 1000 ng D-Trp-6-LH-RH were significant. Naloxone in a dose of 0.5 mg/kg IP totally abolished the inhibition of apomorphine-induced stereotypy by 1000 ng D-Trp-6-LH-RH, but the opiate antagonist did not influence amphetamine-induced stereotypy but significantly potentiated the inhibitory effect of 100 ng D-Trp-6-LH-RH. In the tail-flick test the latencies were significantly increased after D-Trp-6-LH-RH ICV, both 20 or 40 min after the injections. The peptide-induced analgesia was totally naloxone reversible. The results indicate that the agonist analog of LH-RH exert potent actions on the central nervous system, and the mechanism of effects may involve dopaminergic transmission and/or endogenous opiates.     

Gender differences in open-field behavior as a function of age

Male and female rats were observed in an open field at 30, 45, 60, 90, and 120 days of age. Thirty- and 45-day-old rats of both genders presented similar defecation, ambulation, and rearing scores. From 60 days on the male rats showed higher defecation scores and less ambulation and rearing than did the females. The gender difference observed in the adult rats reflected a decrease of defecation by femeles and a decrease of ambulation and rearing by males when compared to the earlier ages.     

Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors

Cannabidiol (CBD) is a major non-psychotropic constituent of Cannabis sativa, with well recognized therapeutic potential. Considering the importance of the endogenous cannabinoid system to the regulation of food intake and energy balance we studied the effects of repeated CBD administration on body weight gains in rats. Male Wistar rats (260 ± 20 g at start of study) received intraperitoneal injections of CBD at doses of 2.5 and 5mg/kg/day for 14 consecutive days and body weight gains were monitored. Both doses of CBD produced significant decrease in body weight gain, with the effect produced by 5mg/kg being more pronounced. The CB2 receptor selective antagonist, AM630, blocked the decrease in body weight gain. AM630 alone did not affect body weight gain. The results suggest that CBD has the ability to alter body weight gain, possibly via the CB2 receptor. CB2 receptors may play a role in the regulation of body weight and the effects of CB2 specific ligands should be further investigated in studies of body weight regulation.     

Effects of early rearing experience on feeding behavior in B6D2F2 mice

This work investigated putative factors contributing to the hyperphagia previously observed in mice which had been overfed during the preweaning period by rearing in small litters. In the first study, B6D2F2 mice, reared in small (Sm = 4), medium (Md = 8) and large (Lg = 12) litters, were subjected to a series of diets adulterated with varying concentrations of sucrose octa-acetate (1, 2, 4, and 8%). All animals reduced their food intake in response to the dietary adulteration, with evidence of a dose-response effect, but this response did not differ as a function of litter size. The second study addressed the involvement of the opioid system in the feeding response through the administration of a series of doses of naloxone (0.1, 0.25, 0.5, 1.0, 2.5, and 5.0 mg/kg, or 5, 7.5 and 10.0 mg/kg). Although naloxone treatment did reduce food intake, there was not a clear dose-response relationship. Again, there was no interaction with litter size. These results do not support effects of early rearing on the feeding response to dietary adulteration or to the effects of naloxone administration.