The influence of cypramil on depressive disorders of behavior in young thyroidectomized male rats

The activity of selective serotonin re-uptake inhibitor cypramil (cipramil, citalopram) has been studied in young male rats with thyroid hormone dysbalance induced by thyroidectomy. Thyroidectomy increased the level of depressed behavior in the Porsolt forced swim test and enhanced the expression of emotional behavior in the open-field test. The replacement treatment of thyroidectomized rats with triiodothyronine (T3) produced an antidepressant and anxiolytic effects. The chronic administration of cypramil also produced an antidepressant action in the Porsolt test, the drug effect being more pronounced in the case of a combined treatment with cypramil and T3 (synergism). Cypramil reduced the horizontal motor activity and the oprientation-research activity in the open-field test, but these drug effects were less pronounced in the case of joint administration with T3.     

Effect of alcohol intake on some disturbances induced by chronic exposure to carbon disulphide in rats. I. Behavioural alterations

Female white Wistar rats were exposed to CS2 vapour (0.8 mg CS2/1 air) 11 months and to 10% ethanol as the only drinking liquid for the last 3 months of exposure. Spontaneous exploratory motor activity (SEMA), open-field behaviour, passive avoidance performance and the avoidance acquisition were tested. Ethanol did not change the exploratory motor activity and behaviour of CS2-exposed rats in the open-field and passive avoidance tests but it affected their performance in the conditioned avoidance test. The analysis of data suggests that ethanol may adversely affect memory and learning ability in CS2-exposed rats.     

Effects of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH on passive and active avoidance behavior and on open-field activity of rats

The action of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH on the passive and active avoidance behavior and open-field activity of rats was studied after peripheral and intracerebroventricular administration. When applied before the test session, intracerebroventricular administration increased the avoidance latency of passive avoidance behavior. Subcutaneous, intraperitoneal and intracerebroventricular administration of the peptide delayed the extinction of active avoidance behavior. Both subcutaneous and intracerebroventricula administration increased the grooming activity of the rats. The data suggest that H-Phe-Ile-Try-His-Ser-Tyr-Lys-OH is able to influence memory, acting mainly on the retrieval processes, ad to modify open-field activity.     

The determination of the optimal dose of milnacipran in the olfactory bulbectomized rat model of depression

Olfactory bulbectomy (OB) is associated with a variety of behavioral abnormalities such as hyperactivity in the "open-field" test. Previous studies have shown that chronic administration of antidepressants can reverse this behavioral deficit. The activity of milnacipran (20, 30, and 40 mg/kg, PO bid) administered in two equally divided doses twice daily was assessed in the olfactory bulbectomized rat model of depression. It was found that chronic treatment with milnacipran at the doses of 30 and 40 mg/kg, but not 20 mg/kg, attenuated the lesion-induced hyperactivity of the OB rat in the "open-field" test following 14 days of treatment. In the step-through passive avoidance test, administration of milnacipran at doses of 20, 30, and 40 mg/kg had no effect on the performance deficit associated with olfactory bulbectomy. Olfactory bulbectomy reduced the concentration of noradrenaline (NA) in the frontal cortex. However, chronic milnacipran treatment did not significantly alter this deficit. It is concluded that milnacipran, when administered chronically at doses of 30 and 40 mg/kg, are effective at reversing the "open-field" deficit associated with olfactory bulbectomy, and that a dose of 30 mg/kg is an optimal dose.     

An experimental study of the psychotropic effects of aspartic acid from the aspect of age

After acute injections to adult and 90-day old rats aspartic acid in doses of 100-500 mg/kg increased the locomotor and exploratory activity during the open-field test and in a dose of 100 mg/kg exerted the antidepressant effect during the forced swimming test. Following treatment for 10 days the amino acid in a dose of 10 mg/kg disrupted acquisition of passive avoidance reaction of young rats and in a dose of 100 mg/kg inhibited learning of active avoidance reaction in adult rats.     

Susceptibility of metallothionein-null mice to the behavioral alterations caused by exposure to mercury vapor at human-relevant concentration.

While recent human studies suggested adverse neurobehavioral outcomes of low-level exposure to mercury vapor (Hg0) as found among those having dental amalgam fillings and dental personnel, past animal experiments only dealt with exposure at much higher mercury concentrations. The present study aimed to examine neurobehavioral effects of prolonged, low-level Hg0 exposure in mice and to evaluate the protective role of metallothionein-I,II (MT-I,II) against Hg0-induced neurotoxicity, using a knock-out strain of mice. Adult female metallothionein-I,II-null (MT-null) and wild-type OLA129/C57BL6 mice were exposed to 0.06 mg/m3 of Hg0 for 8 h per day for 23 weeks. Neurobehavioral effects were evaluated at 12 and 23 weeks of exposure using open-field test and passive avoidance test. Subcellular distribution of mercury and the induction of MT were also assessed. The Hg0 exposure resulted in significantly enhanced locomotion in the open-field test and poorer performance in the passive avoidance test at a brain Hg concentration less than 1 ppm. These effects were slightly exaggerated in MT-null mice, which showed less induction of MT, lower brain Hg concentration, and lower calculated concentration of MT-unbound cytosolic Hg. The results showed, for the first time, that a concentration of Hg0 relevant to human exposure level could cause neurobehavioral effects in adult mice. The higher susceptibility of MT-null mice suggested that MT-I,II have protective roles in the metal-induced neurobehavioral toxicity, which cannot be entirely explained by kinetic mechanisms, thus suggesting an involvement of nonkinetic mechanisms.     

Prenatal exposure to dichlorvos: physical and behavioral effects on rat offspring

The effects of prenatal exposure to dichlorvos (DDVP), an organophosphate (OP) pesticide, on pups' physical and neurobehavioral developments were investigated. Forty pregnant rats were treated by gavage with 8.0 mg/kg DDVP or its vehicle (1 ml/kg) from the 6th to the 15th day of pregnancy. At birth, pups were weighed, the litters culled to eight animals (four male and four female), and then observed for physical (pinna detachment, incisor eruption, eye opening, testes descent, and vaginal opening) and neurobehavioral developments (palmar grasp, surface righting, negative geotaxis, and open-field behaviors). As adults, open-field, apomorphine-induced stereotypy, and passive avoidance behaviors were also assessed. Results showed no differences between the body weight of DDVP and control-treated groups. No differences were observed on the measures of physical and neurobehavioral development. Locomotor activity of male pups at 21 days of age was decreased by DDVP exposure. Adult experimental offspring showed a decreased locomotor frequency and an increased immobility duration on open-field behavior in relation to control animals; the apomorphine-induced stereotyped behavior was decreased by the pesticide exposure as well as performance on the passive avoidance task. These data suggest that prenatal DDVP exposure was able to decrease offspring motor function (adolescence and adults) and conditioned response learning, probably by interference with the cholinergic-dopaminergic balance of activity involved with the control of motor function as well as the cholinergic system that modulates learning process.     

Combined action of uranium and stress in the rat. I. Behavioral effects

The influence of restraint stress on uranium (U)-induced behavioral effects was assessed in adult male rats. Eight groups of animals received uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 10, 20 and 40 mg/kg/day during 3 months. Rats in four groups were concurrently subjected to restraint during 2 h per day throughout the study. At the end of the period of uranium exposure, the following behavioral tests were carried out: open-field activity, passive avoidance and Morris water maze. Uranium concentrations in brain were also determined. At 10 and 20 mg/kg/day of UAD restraint significantly affected the total distance traveled in the open-field during the first and third periods tested, respectively, while no significant differences between groups were observed on the passive avoidance test. In the Morris water maze test, the influence of restraint was only significant on the latency time measured on Day 3 in rats exposed at 10 mg/kg/day. Restraint stress did not affect significantly the uranium levels in brain of rats. Although the results of the present study scarcely show uranium-induced behavioral effects at the oral doses of UAD here administered, these effects, as well as the slight influence of restraint stress noted in some tests should not be underrated.     

Errata

The effect of novel potent CCK-8 antagonists on a one-trial passive avoidance response was investigated in the rat. Intracerebroventricular administration of L-364,718 and CR 1409 in doses of 10 ng per rat or more and proglumide in doses of 100 ng per rat or more completely attenuated the passive avoidance response, when examined 24 hr after the injection. The effective doses of these antagonists did not cause any motility change, as tested by an open-field situation at the same period of time after the central administration. The present findings, together with our previous results on an active avoidance response, suggests that endogenous CCK-8 may be involved in memory processes.     

Effects of chlordane on conditioned avoidance response, brain seizure threshold and open-field performance of prenatally-treated mice

1. Three groups of six pregnant albino mice at the third stage of gestation were given chlordane 1 or 2.5 mg/kg body weight or olive oil 10 ml/kg. They were dosed orally for seven consecutive days.2. Ten young mice, regardless of sex, were randomly selected from the progeny of each group of treated mothers and tested for conditioned avoidance response, electroshock seizure threshold, and open-field performance.3. Offspring of chlordane-treated mice made fewer conditioned avoidance responses than the controls on each day of training.4. Electroshock seizure threshold was raised.5. In the open-field test, progeny of mothers receiving the larger dose were more active than controls. A dose x days interaction indicated a complex response of the chlordane-treated mice to experience in the open-field.6. The significance of these findings is discussed.     

The interaction between β-[Tyr9]melanotropin-(9–18), haloperidol and amphetamine in different behavior tests of rats

The effects of β-[Tyr⁹]melanotropin-(9–18) on the extinction of the active avoidance reflex in (dopamine receptor blocker) haloperidol-treated animals, and on the open-field activity in haloperidol and amphetamine-treated rats were studied. It was shown that a systemically given 100 ωg dose of the peptide, which had no action on the ambulation and rearing activity in the open-field test, could still delay the extinction of the active avoidance reflex. Haloperidol treatment was able to partially block the effects of the ICV administered β-[Tyr⁹]melanotropin-(9–18) on both the extinction and open-field activity. After intracerebroventricular administration, the effect of the peptide on the open-field test was partially similar to that of amphetamine: it facilitated the ambulation and rearing activity, and (in contrast with amphetamine) was able to facilitate the grooming activity, even in the presence of amphetamine. The results suggest that dopaminergic innervation might play a mediating role in the effect of β-[Tyr⁹]melanotropin-(9–18) on the extinction of the active avoidance reflex and open-field activity. The effect on the open-field activity differens in part from that of amphetamine.     

Combined action of thioperamide plus scopolamine, diphenhydramine, or methysergide on memory in mice.

The aim of the present experiments was to test the role played by the interaction of the selective H3 receptor antagonist, thioperamide, with the cholinergic, histaminergic, and serotonergic systems in modifying memory. The behavioral tests used (open-field and passive-avoidance repetition) were selected on the basis of the action displayed by thioperamide in these behavioral situations. Posttrial administration of thioperamide (5 mg/kg) resulted in an improvement in memory consolidation, as tested in the repetition of the open-field test, but repeated posttrial administration of thioperamide (2 or 5 mg/kg) had no effect in the repetition of passive avoidance test. Scopolamine (2 mg/kg) caused a deterioration in the memory processes in both tests: this effect was blocked by 2 mg/kg of thioperamide, which was itself ineffective in the test. These results may suggest that both the improvement in memory due to thioperamide and its antagonism of the amnestic effects of scopolamine are determined by activation of central cholinergic systems, due to thioperamide inhibition of H3 heteroreceptors. Diphenhydramine (2 or 10 mg/kg) was itself ineffective in the tests, but counteracted the memory improvement caused by thioperamide in the repetition of the open-field test. The effect of diphenhydramine is discussed in terms of interactions between histaminergic and cholinergic systems. Methysergide counteracted the effect of thioperamide in the open-field test only at a high dosage (50 mg/kg). The possible implication of serotonergic systems on the effects of the methysergide-thioperamide interaction in the memory process is discussed.     

Cycloheximide induced amnesia and recovery as a function of training parameters

Mice were given 2 or 3 training trials in a passive avoidance task following an injection of cycloheximide or saline. They were tested 1, 1.5, 3, 24, or 72 hr after training and tested again 72 hr after the first test trial. All the cycloheximide groups except the 1 hr groups were inferior to saline controls on the first test trial, and there was no suggestion of spontaneous recovery over the intervals tested. Test 2 performance was generally inferior to Test 1 performance for all groups, but the cycloheximide groups showed the greatest drop in performance. A second experiment extended train/test intervals to 144, 146, 148, and 192 hr. Spontaneous or test induced recovery again did not occur. The discussion attempts to reconcile these results with prior reports of recovery in terms of differential conditioning of different components of passive avoidance memory by the different training procedures. This results in partial sparing of some components of passive avoidance memory by cycloheximide, which has the appearance of recovery under certain test conditions.     

Amiridine (NIK-247) and cerebrocrast in the alleviation of cholinergic lesion-induced learning deficit in male rats

Learning of the male rats was impaired by injecting ethylcholine aziridinium (AF64A) bilaterally into the basal magnocellular nuclei of Meynert. The performance of the rats in a passive avoidance test and in a one-way active avoidance test was significantly improved by giving a novel acetylcholinesterase inhibitor, amiridine (NIK-247; 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)-quinoline monohydrate hydrochloride) after each learning session but not when the drug was given before the sessions. Cerebrocrast, an antagonist of L-type calcium channels, was not effective in either case. Rather it worsened the learning results when given after the sessions of the active avoidance test. The conclusions in the passive avoidance test were hampered by the observed inconsistent effects of cholinotoxin. © 1993 wiley-Liss, Inc.     

Enhanced learning of normal adult rodents by repeated oral administration of soybean transphosphatidylated phosphatidylserine

Soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) is already known to improve the learning ability of aged or drug-induced amnesic rodents. In this study, its effect on normal adult rodents was evaluated using several learning tasks. Firstly, three behavioral tests (open-field, Y-maze, and active avoidance test) were consecutively carried out after the daily oral administration of SB-tPS (50 mg/kg per day, for 34 days). Repeated oral administration of SB-tPS did not affect either exploratory behavior in the open-field test or spontaneous alternation behavior in the Y-maze test, while mice pretreated with SB-tPS showed significant enhancement of conditioned avoidance response. Secondly, the brightness discrimination test was used to evaluate the effect of SB-tPS on learning ability. The daily oral administration of SB-tPS (50 mg/kg per day, for 27 days) to normal rats significantly increased the correct response ratio in the brightness discrimination test. Finally, to elucidate the necessity of SB-tPS pretreatment, another active avoidance test was carried out, and no enhancement of conditioned avoidance response was observed in non-pretreated mice. These results suggest that repeated administration of SB-tPS could enhance the learning ability of normal adult rodents as those of aged ones.     

大鼠嗅球切除抑郁症动物模型的改进与评价

目的改进大鼠嗅球切除(olfactory bulbectomy,OB)抑郁症动物模型的建立方法并评价模型的可行性。方法应用探针捣毁嗅球与负压吸引相结合的方法进行嗅球切除,恢复2周后分组:假手术组、嗅球切除模型组、氟西汀(10 mg.kg-1,ig,每天1次,14 d)治疗组。给药2周后通过开场实验、蔗糖饮水实验和逃避实验检测各组大鼠的行为学。结果与假手术组比较,嗅球切除模型组大鼠开场实验水平运动得分和垂直运动得分明显增多,蔗糖偏嗜度明显降低,逃避失败次数明显增多,长期氟西汀治疗能够逆转嗅球切除引起的行为学改变。结论大鼠嗅球切除后出现抑郁样行为学改变,经典抗抑郁药物治疗有效,通过改进建立了稳定的大鼠嗅球切除抑郁症动物模型及可靠的评价方法。     

Effect of corticosteroids in the hippocampus on passive avoidance behavior in the rat

The site of action of corticosteroids in avoidance learning was investigated in 110 rats. Injection of cycloheximide, 30 min before one-trial training on a passive avoidance task suppressed corticosteroid secretion in response to footshock, and produced an avoidance deficit in a test 6 days later. However, an additional injection of hydrocortisone, either subcutaneously or intra-hippocampally within 5 min of training, restored the avoidance response in the test. Septal and hypothalamic injections of the hormone were ineffective in reversing the cycloheximide effect, whereas the effect of hormone injection into the amygdala was equivocal because of an increased level of activity. Corticosteroids secreted following an aversive experience appear to act upon the steroid-sensitive neurons in the hippocampus to influence the animal's later performance of passive avoidance response.     

Fetal alcohol effects in long- and short-sleep mice: activity, passive avoidance, and in utero ethanol levels

Genetic differences in susceptibility to fetal alcohol effects (FAE) have been suggested by both human and animal studies. The Long-Sleep (LS) and Short-Sleep (SS) mouse lines, selectively bred for differences in ethanol-induced narcosis, provide a model for studying differential alcohol sensitivity in the etiology of FAE. LS and SS mice were intubated with either 2.9 g/kg (20% w/v) ethanol (E) or an isocaloric amount of sucrose (S) twice per day (6 hr apart) on Days 7 through 15 of pregnancy. An untreated control group (C) was maintained for each line. Offspring were fostered to lactating Rockland-Swiss mice at birth. LS offspring prenatally exposed to ethanol exhibited increased open-field activity relative to LS controls, but this effect was due to the overactivity of one litter. Activity for SS mice prenatally exposed to ethanol did not differ from control levels. Ethanol content in blood (280 mg/dl), amniotic fluid (258 mg/dl), and fetal tissue (230 mg/dl) did not differ in similarly treated LS and SS dams. In a second experiment, females were treated from Days 7 through 18 of gestation, and their offspring were tested for either open-field activity or passive avoidance learning. There were no group differences in open-field activity, but LS mice prenatally exposed to alcohol took more trials to reach a passive avoidance criterion than their controls, whereas similarly treated SS mice did not differ from controls. These results suggest that genetically-mediated sensitivity to ethanol influences susceptibility to FAE and that this may be task specific.     

前胡提取物对抑郁症模型大鼠脑内中枢单胺类神经递质的影响研究

目的：研究前胡提取物中香豆素类化合物对抑郁症模型大鼠脑内中枢单胺类神经递质的影响。方法以孤养加慢性轻度不可预见性应激方法建立大鼠抑郁症模型,测定糖水消耗、敞箱行为及跳台行为来进行行为学评分,并采用高效液相－电化学方法检测其脑内单胺类神经递质的含量,观察模型大鼠给药前后的变化。结果抑郁症模型组大鼠体质量增长缓慢,蔗糖水消耗量明显下降,水平活动和垂直活动均显著下降,跳台错误次数增加,脑内的去甲肾上腺素、5－羟色胺含量降低（P＜0．05）。30mg／（kg? d）、50mg／（kg? d）剂量前胡提取物能显著改善模型大鼠的行为学变化,增加其脑内去甲肾上腺素、5－羟色胺含量（ P＜0．05）。结论前胡提取物中香豆素类化合物具有抗抑郁作用,对中枢单胺类神经递质的调节作用是其作用机制之一。     

小鼠对新环境和回避反应的记忆特征:开阔行为和避暗实验比较(英文)

目的:研究小鼠对新环境和回避反应记忆特点.方法:用开阔和避暗实验.结果:小鼠对开阔环境记忆仅保持48 h,对回避反应记忆持续96 h以上.在开阔和回避反应实验中,小鼠获得记忆所需的学习时间分别为0.5和2min.东莨菪碱,氯丙嗪,异丙嗪,印防己毒素,咖啡因和戊巴比妥能抑制小鼠回避反应.但小鼠对开阔环境的记忆仅被东茛菪碱和咖啡因阻断.结论:与回避反应相比,小鼠对新环境的记忆表现为易获得,易消退,不易被药物阻断.