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.     

Avoidance performance,cue and response-choice discrimination after neuroleptic treatment

The effects of pimozide on discriminated avoidance performance in a Y-maze were evaluated in mice. Relatively low doses of pimozide (0.4 mg/kg) retarded acquisition of an active avoidance response. The avoidance deficit induced by this dosage was largely eliminated among mice tat had received either 1 or 2 previous avoidance training sessions, but was still evident in mice treated with a higher drug dosage (0.8 mg/kg). If mice were initially trained in the drug condition, the disruptive effects were still evident in a later test conducted in the absence of the drug treatment. In contrast to the avoidance deficits, pimozide did not disrupt the acquisition or the performance of a cue- or response-choice discrimination. That is, once a running response was initiated (on avoidance trials) pimozide treated animals appeared capable of appropriately directing the response. It is suggested that at the dosages used pimozide did not affect S-S learning or learning response-outcome contingencies, but rather hindered performance owing to deficits in response initiation processes. Moreover, within a task involving aversive motivation pimozide did not appear to reduce the reinforcement derived for correct responding.     

Learning impairment following acute administration of the calcium channel antagonist nimodipine in mice

The effects of acute systemic administration of the Ca(2+) channel antagonist nimodipine were examined on learning capacities of adult Swiss mice. Tests included spontaneous alternation behaviour, for spatial working memory; and step-down passive avoidance and place learning in a water maze, for long-term memory. Nimodipine markedly impaired spontaneous alternation at doses of 0.3-1mg/kg i.p., and passive avoidance at doses of 0.3-3mg/kg i.p., as compared to the vehicle-treated animals. At 0.3mg/kg i.p., the drug did not alter motility in an open field, but significantly decreased performances in training trials and retention in the water maze. Subchronic nimodipine 0.3 and 1mg/kg once a day i.p. for 10 days) did not affect performances in the Y-maze and passive avoidance tests. These results show that acute nimodipine administration alters learning in adult mice, and argue for an involvement of voltage-dependent Ca(2+) channels in learning.     

The effect of chronic administration of trazodone on the acquisition of avoidance behavior in mice

An atypical antidepressant trazodone, given in doses of 5 or 10 mg/kg ip during the period of avoidance training (15 min before the beginning of each of 5 consecutive daily sessions) significantly depressed the rate of acquisition of the conditioned avoidance response. However, in mice pretreated with trazodone, 10 mg/kg daily for the preceding 14 consecutive days, the treatment with 10 mg/kg before each session did not impair the acquisition of the conditioned avoidance response, and the treatment with a dose of 5 mg/kg improved the acquisition over the control level. The data show that the pattern of action of trazodone on the acquisition of conditioned avoidance response is the same as that of other antidepressant agents, desipramine and mianserin, and indicate that chronically administered antidepressant agents do not impair learning.     

Protective Effect of Arabinoxylan against Scopolamine-Induced Learning and Memory Impairment

The purpose of this study is to investigate the memory enhancing effect and underlying molecular mechanism of arabinoxylan (AX), a major component of dietary fiber in wheat against scopolamine (SCO)-induced amnesia in Sprague-Dawley (SD) rats. Diverse behavior tests including Y-maze, Morris water maze, and passive avoidance tests were performed to measure cognitive functions. SCO significantly decreased the spontaneous alterations in Y-maze test and step-through latency in passive avoidance test, whereas increased time spent to find the hidden platform in Morris water maze test compared with the sham control group. In contrast, oral administration of AX (25 mg/kg and 50 mg/kg) effectively reversed the SCO-induced cognitive impairments in SD rats. Furthermore, AX treatment up-regulated the expression of brain-derived neurotrophic factor (BDNF) in the cortex and hippo-campus via promoting activation of cAMP response element binding protein (CREB). Therefore, our findings suggest that AX can improve SCO-induced learning and memory impairment possibly through activation of CREB and up-regulation of BDNF levels, thereby exhibiting a cognition-enhancing potential.     

知母皂苷元及其异构体对老年大鼠学习记忆和脑内M_1受体密度的影响

目的　观察知母皂苷元 (ZMS)及其异构体 (ZMR)对老年大鼠学习记忆和脑内M1受体密度的作用。方法　选择 2 4mon龄SD老年大鼠 ,将动物分为老年对照组、ZMS组和ZMR组 ,并以 3～ 4mon龄青年大鼠作为正常对照 ,用迷宫法测定学习记忆能力 ,采用放射配基结合分析法测定脑内M1受体密度。结果　用药组大鼠连续口服ZMS和ZMR 4 0d后 ,与老年对照组比较 ,其学习记忆能力明显增强 ,脑内M1受体密度升高。结论　知母皂苷元及其异构体对老年性痴呆的胆碱能系统功能渐进性退化有一定的预防和治疗作用     

Anti-amnesic effect of prolyl endopeptidase inhibitors in mice

Based on the results of a previous report that prolyl endopeptidase (PPCE) inhibitors facilitated the acquisition of active avoidance response and retarded the extinction of the response, further studies were made on the effect of PPCE inhibitors on learning and the memory process. Using mice, tests were performed both in the light-dark discrimination Y-maze task and the lever-press task of the water reinforcement schedule, and mice were also tested in the acquisition and retention of one-trial "step-through" passive avoidance task. The effect of PPCE inhibitors were investigated both in control and electroconvulsive shock- or scopolamine-induced amnesic animals. Z-Pro-p, the most potent inhibitor among 5 compounds tested in this study, and arginine vasopressin (AVP) facilitated the learning process and retarded the extinction of the acquired response in all tests. Suc-Pro-p was also effective in the Y-maze and passive avoidance test. Thus, the effect of the test compounds were parallel with their in vitro activities as PPCE inhibitor. These results suggest that the anti-amnesic effect of PPCE inhibitors is partially attributable to their effect on the breakdown of the biologically active peptides which are involved in the memory process, such as AVP, in the brain.     

Amphetamine and the overtraining reversal effect

Rats were trained in a Y-maze on a two choice simultaneous brightness discrimination with light as S+ and dark as S- (position irrelevant). Animals in the Mastery group were trained until they reached criterion and were then switched to reversal, where the reinforcement contingencies of the original training were reversed. Animals in the Overtraining group received a further 110 trials before being switched to reversal. The administration of 1 mg/kg d-amphetamine facilitated dramatically reversal learning in Mastery group. Overtraining improved reversal in saline injected animals and slowed down reversal in amphetamine-treated animals. The drug also facilitated the acquisition of the initial brightness discrimination.     

Effect of late fetal irradiation on adult behavior of mouse: Dose-response relationship

Pregnant Swiss mice were exposed to 0.3-1.5 Gy of gamma radiation on day 17 of gestation and allowed to deliver the offspring. When the F1 mice were 6 months old, they were subjected to a number of behavioral tests. Open-field and dark-bright arena tests were conducted to study locomotor and exploratory activities. Learning and memory were tested by holeboard activity, conditioned avoidance response, and radial arm maze performance. After all the tests, 20 animals (10 males and 10 females) from each group were killed, and their brain weight was taken. The open-field and dark-bright arena tests showed a significant dose-dependent decrease in the locomotor and exploratory activities. Reduction in time spent in the dark area and higher locomotor activity in the bright area indicated a reduced aversion to bright light. But the emotional activities like rearing and grooming did not change. The learning and memory functions also showed a significant impairment, even at 0.3 Gy. The deficit in the performance in the holeboard test, conditioned avoidance response, as well as maze-learning efficiency, decreased linearly with increase in radiation dose. The brain weight showed a linear dose-dependent decrease. But the brain/body weight ratio was not significantly affected even at 1.5 Gy. These results demonstrate that exposure of a mouse on day 17 of gestation to radiation doses below 1.0 Gy can induce significant impairment in the adult brain function, without producing any notable effects on brain morphology. This study also suggests that the retardation of higher brain function by exposures during the late fetal period may have a threshold of around 0.3 Gy.     

Simultaneous brightness discrimination and reversal: the effects of amphetamine administration in the two stages

Rats were trained in a Y-maze on a two-choice simultaneous brightness discrimination with light as S+ and dark as S- (Stage 1), and were then switched to reversal, where the reinforcement contingencies of the original training were reversed (Stage 2). d-Amphetamine, 1 mg/kg, was administered in a 2 X 2 design, i.e., drug-no drug in Stage 1 and drug-no drug in Stage 2. The administration of the drug in Stage 1 improved the acquisition of the initial brightness discrimination and facilitated reversal learning independently of the drug administered in Stage 2. In addition, the administration of the drug in Stage 2 only improved performance towards the end of reversal training. The results indicate that amphetamine enhances the attention to, or the associability of, the discriminative stimuli, leading to a rapid learning to these stimuli under changed contingencies of reinforcement.     

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.     

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 an extract of Ginkgo Biloba (EGB 761) on "learned helplessness" and other models of stress in rodents

The effects of repeated oral administration of an extract of Ginkgo Biloba (EGB 761) on various behavioral models of stress in rodents were investigated. The models in rats included "learned helplessness," shock-suppressed licking (Vogel conflict test) and forced swimming-induced immobility ("behavioral despair"). The models in mice included shock-suppressed exploration (four plates test), spontaneous exploration (staircase test) and food consumption in a novel situation (emotional hypophagia). Further tests in rats examined the effects of EGB 761 on memory (passive avoidance test) and responsiveness to shock to determine whether the preventive effects observed with EGB 761 in the learned helplessness procedure were due either to drug-induced impairment of memory or to reduced shock sensitivity. In all experiments EGB 761 was administered over 5 days at daily doses of 50 and 100 mg/kg PO. In some experiments (Vogel test, four plates test, staircase test, emotional hypophagia) the effects of acute administration were also investigated. The results showed that repeated administration of EGB 761 (50 and 100 mg/kg/day) before exposure to unavoidable shock (preventive treatment) clearly reduced the subsequent avoidance deficits in the learned helplessness procedure but was less effective when first administered after "helplessness" induction (curative treatment). EGB 761 did not affect performance in the passive avoidance task or alter the animals' response to electric shock, suggesting that the effects observed in the learned helplessness procedure were not due to impaired memory or reduced shock sensitivity. Anxiolytic-like activity was also seen in the emotional hypophagia test in mice where repeated administration of EGB 761 increased the amount of food consumed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of propentofylline on disorder of learning and memory in rodents

Effects of a newly synthesized xanthine derivative propentofylline (3,7-dihydro-3-methyl-1-(5-oxohexyl)-7-propyl-1H-purine-2,6-dione) on learning and memory of rodents were examined in the two different paradigms. In a shuttle box active avoidance paradigm, propentofylline (25 mg/kg/day, p.o.) improved the decreased learning ability of 12-month-old spontaneously hypertensive rats. Normotensive Wistar-Kyoto rats at a comparable age showed rapid acquisition of avoidance learning, which was not influenced by propentofylline. Step-down passive avoidance task was carried out as the other paradigm. The protein synthesis inhibitor cycloheximide (CXM) induced amnesia in young adult mice. Propentofylline improved the memory deficit when intraperitoneally administered 30 min before the retention test, and it also prevented the development of amnesia when injected 15 min before CXM. These results suggest that propentofylline ameliorates the disturbed learning and memory.     

吗啡增强谷氨酸对小鼠的神经毒性

新生期小鼠sc谷氨酸单钠(MSG)后能使下丘脑弓状核及其它脑室周围结构神经元坏死。预注吗啡可明显增强MSG的神经毒性作用,使弓状核的神经元坏死数增加。新生期小鼠sc MSG或吗啡+MSG均能破坏动物成年后Y型迷宫分辨学习能力,但对分辨学习的保持(retention)无影响。吗啡+MSG还使动物被动回避反应的保持及脑Ca~(2+)水平明显下降。纳洛酮能逆转吗啡的增强效应。吗啡+MSG引起的脑损伤、学习记忆缺陷(deficiency)及脑Ca~(2+)水平下降三者之间具有明显的平行关系。     

Effects of prenatal rubratoxin-B exposure on behaviors of mouse offspring.

The effects of prenatal rubratoxin-B (RB) exposure on 8 behavioral parameters in JCL:ICR mice were assessed. Pregnant mice were injected intraperitoneally with 0.1 or 0.2 mg/kg/day of RB dissolved in propylene glycol water solution on days 7-9 (Group A) or 10-12 (Group B) of gestation. Controls received the vehicle similarly on days 7-12 of gestation. Before weaning, the offspring of both sexes were examined to test their the surface righting reflex (5 days of age), cliff avoidance response (6 days), negative geotaxis response (7 days), and swimming development (8, 10, and 12 days). After weaning, male animals were examined using the rotarod test (6 weeks of age), the open-field test (7 weeks), the shuttle-box-avoidance-learning test (9 weeks), and the water E-maze test (10 weeks). The preweanling offspring in the 0.2 mg/kg-B group showed significantly lower success rates and longer response times than controls in the cliff-avoidance response. In swimming development, the offspring in the 0.2 mg/kg B group had significantly lower scores than controls for swimming angle at 10 and 12 days of age. The avoidance learning of the mice in all RB-exposed A and B groups was significantly poorer than that of controls. These results indicate that prenatal exposure to RB produced a delay of early response development and impaired learning ability in the offspring of mice exposed to RB during middle pregnancy.     

Features of memantine action profile in cholinergic deficit and intracerebral posttraumatic hematoma (hemorrhagic stroke) models in rats

Memantine, a low-affinity non-competitive antagonist of glutamatergic NMDA-subtype receptors, was used at a daily dose of 1 mg/kg over 10 days for the treatment of rats with cholinergic deficit induced by the chronic administration of scopolamine (1 mg/kg, 20 days). The drug prevented violation of the learning of conditioned active and passive avoidance reflexes and produced no significant effect on the emotional state of animals in elevated plus maze (EPM) test. In animals with intracerebral posttraumatic hematoma (hemorrhagic stroke), memantine (2 mg/kg, for 3 days after operation) completely prevented the loss of animals, reduced the neurological deficit, improved conditioned passive avoidance reflex performance, and decreased emotional stress in the EPM test.     

Effects of systemic administration of beta-casomorphin-5 on learning and memory in mice

The effects of systemic administration of bovine beta-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), a mu-opioid receptor agonist derived from milk beta-casein, on spontaneous alternation behavior in the Y-maze (spatial short-term memory) and step-down-type passive avoidance response (non-spatial long-term memory) were investigated in mice. Intraperitoneal (i.p.) administration of beta-casomorphin-5 (0.1-20 mg/kg) did not have a significant effect on either spontaneous alternation behavior or passive avoidance response. However, a low dose (1 mg/kg, i.p.) of beta-casomorphin-5 improved scopolamine (1 mg/kg, s.c.)-induced impairment of spontaneous alternation behavior and passive avoidance response. Pretreatment with intracerebroventricular injections of beta-funaltrexamine (a mu-opioid receptor antagonist, 0.1 microg/mouse) and naloxonazine (a mu(1)-opioid antagonist, 5 microg/mouse), which did not improve scopolamine-induced impairment, prevented the ameliorating effect of beta-casomorphin-5 on scopolamine-induced impairment of passive avoidance response. These results indicated that systemic administration of a low dose (1 mg/kg, i.p.) of beta-casomorphin-5 improves the disturbance of learning and memory resulting from cholinergic dysfunction through central mediation involving mu(1)-opioid receptors.     

Technique for assessing visual discrimination learning in mice

An automated technique for the study of visual discrimination learning in mice has been developed. The technique utilizes a nose-poke as the operant response. The nose-poke response requires no shaping, has a relatively high operant level and can be used to measure preacquisition exploratory behavior. CD-1 mice acquired a simultaneous brightness discrimination readily but a successive brightness discrimination proved more difficult. A 20 sec intertrial interval was optimal for acquisition of the simultaneous discrimination. Reversal learning was slow. This procedure should prove useful in the study of the effects of pharmacologic and toxic agents on learning and performance in both weanlings and adult mice.