Vasopressin levels in peripheral blood and in cerebrospinal fluid during passive and active avoidance behavior in rats.

Vasopressin (AVP) levels were measured in plasma and cerebrospinal fluid (CSF) of rats during acquisition and retention of a passive avoidance response. Only 5 min after the onset of the retention session a significantly higher level of AVP was found in plasma of animals which displayed a long latency, as compared with the levels of animals which showed a weak passive avoidance response (short latencies), or no passive avoidance behavior at all (controls). Moreover no changes in plasma AVP levels were found in plasma of rats submitted to acquisition or extinction of an active avoidance response. It is suggested that, although an elevated plasma AVP level is associated with strong retention of a passive avoidance response the peripheral circulation as well as the CSF are of minor importance for the transport of this neuropeptide to its site of behavioral action.     

The active avoidance reaction of laboratory rats: differences between experiments carried out in the phase of motor activity and inactivity

The influence of two phases of the circadian cycle (motor activity and motor inactivity) on the rate of acquisition and extinction of an active avoidance reaction was studied in 35-day-old male laboratory rats reared in cages (with limited social contacts), in young reared from the age of 15 days in communities (with the broad social contacts typical of this species) and in adult males reared in cages. A difference was found between the results of experiments carried out in the morning (during the motor inactivity period) and in the early evening (at the outset of the motor activity period) in both young and adult animals. The factor deciding whether acquisition or extinction was influenced depended on the mode of life. In animals reared in cages, inhibition was influenced; extinction was elaborated faster in the evening in adult animals and juvenile young were capable of 100% extinction only in the evening (in the morning only 50%). Community young achieved 100% extinction in both cases. In young rats which lived in a community from the 15th day, acquisition was influenced (it was achieved faster in the evening). The correlation between the rate of acquisition and extinction in cage-bred adult and young rats was negative if the experiments were carried out in the morning and was positive in evening experiments on young animals. In community-bred young it was positive in both cases.     

Vasopressin deficiency and blood glucose interactions on passive avoidance behavior

The performance of a passive avoidance task (measured for two trials based upon number of complete step-downs and latency to respond) and blood glucose levels were examined in five groups of animals. The groups included vasopressin-deficient (DI) and vasopressin-containing (LE) rats under ad lib (AL) and food-restricted (FR) conditions, as well as DI-FR animals provided with access to an 8% sucrose solution (SUC). In the AL condition, no significant differences were found between DI and LE animals in either step-down occurrences or blood glucose levels. However, the DI animals were significantly slower in latency to respond in trial 1. With FR, the LE animals resembled the LE-AL animals in both passive avoidance behavior and blood glucose levels. The DI-FR animals that were not provided with SUC showed an impairment in passive avoidance behavior and low blood glucose levels, whereas DI-FR animals provided with SUC showed an amelioration of passive avoidance deficiencies and had blood glucose levels comparable to AL animals and LE-FR animals. On trial 2, a significant negative correlation was found between number of step-down occurrences and blood glucose levels, and a significant positive correlation was found between latency to respond and blood glucose levels. The experiment demonstrates that: 1) because DI rats have a different responsiveness in novel situations, caution must be exercised in using response latency as a measure of passive avoidance performance in the AL condition; 2) AL and FR conditions produce different responses in DI, but not LE, animals; 3) deficiencies in passive avoidance behavior in DI-FR rats can be ameliorated by the consumption of exogenous carbohydrate; and 4) there is a significant correlation between blood glucose levels and passive avoidance behavior.     

Effects of α-MSH and melatonin on passive avoidance and on PA-induced defecation and plasma 11-OHCS in hypophysectomized rats

The present study shows that α-MSH facilitates the acquisition and delays the extinction of a Passive Avoidance Response (PAR) in the hypox animals. MSH exacerbates PA-induced defecation in both hypox and sham-hypox animals. Hypox and sham-hypox animals treated with MSH do not differ on PAR or on PA-induced defecation. Melatonin, on the other hand, has no significant effect on PAR in hypox rats, but retards acquisition and facilitates extinction of the PAR in sham-hypox rats. Melatonin also inhibits PA-induced defecation in sham-hypox rats. Sham-hypox and hypox rats treated with Melatonin do not differ on PAR learning, retention (Extinction) and PA-induced defecation. MSH and Melatonin also seem to have opposite effects on plasma 11-OHCS levels measured at the end of PAR extinction. MSH increases plasma 11-OHCS in hypox rats, whereas Melatonin decreases plasma 11-OHCS in sham-hypox rats. Melatonin does not lower further the very low level of plasma 11-OHCS in hypox rats.     

Effects of Nicotine and Cytisine on the Formation and Extinction of the Conditioned Active Avoidance Reflex in Rats

We studied the effects of nicotine and cytisine injected i.p. in equimolar doses (0.5 mol/kg) on the formation and extinction of the conditioned active avoidance reflex (AAR) in rats; a combination of conditioning acoustic stimulation and unconditioned nociceptive electrocutaneous stimulation was used for training. A stable AAR was formed more rapidly in the case of nicotine injections; the corresponding effect of cytisine injections did not attain a significance level (probably because of the weak effect of this cholinomimetic on AAR formation in slowly trained animals present in the tested group). Injections of both nicotine and cytisine in the course of formation of a stable AAR led to a significantly slower extinction of the conditioned reflex habit. Both cholinomimetics demonstrated such an effect with respect to both the entire animal population and rats with rapid extinction of the habit. Cytisine-induced slowing down of extinction of the AAR was more significant than the corresponding effect of nicotine. We postulate that the positive effects of cytisine and nicotine on maintenance of the AAR are mediated by activation of neuronal nicotine cholinoreceptors having the ₃₄ subunit structure.     

Involvement of 5-HT1A receptors in passive avoidance learning in intact and ovariectomized female rats

The influence of chronic administration of 5-HT1A receptor agonist 8-OH-DPAT (0.05 mg/kg, s.c.) and 5-HT1A receptor antagonist NAN-190 (0.1 mg/kg, i.p.) injected for 14 days alone or in combination with 17beta-estradiol (0.5 microg i.m./rat/day) was studied on passive avoidance performance (PAR) and on behavior in the open field test in adult intact and ovariectomized (OVX) female rats. Administration of 5-HT1A receptor antagonist NAN-190 alone significantly improved PAR (p<0.05) in intact females with proestrus and estrus and in OVX females. Administration of 5-HT1A receptor agonist 8-OH-DPAT alone or in combination with 17beta-estradiol significantly (p<0.05) improved PAR in OVX rats and failed to normalize PAR in intact rats with proestrus and estrus. Results of the work specify the involvement of 5-HT1A receptors in the mechanisms of passive avoidance learning in OVX female rats.     

Effect of sexual steroids and androgen sterilization on avoidance and exploratory behaviour in the rat

The effect on avoidance and exploratory behavior of large doses of sexual steroids or of changes in ovarian steroid secretion induced by gonadotropin treatment or androgen sterilization was studied in female R-Amsterdam rats. Estrogen, progesterone, testosterone, androgen sterilization, and human chorionic gonadotropin (HCG) effects were tested and evaluated. Estrogen in castrated female rats delayed extinction of the conditioned avoidance response from Day 8 of extinction and increased intertrial activity during extinction. Estrogen treatment applied from extinction was ineffective. Progesterone treatment of castrated female rats applied from the first days of conditioning delayed extinction from Day 12. If the treatment was begun at extinction, this was delayed after Day 8. Intertrial activity was also higher between Day 8 and Day 15 of extinction. Testosterone treatment of castrated male rats increased intertrial activity during acquisition. In the animals treated from extinction, a delay was observed from Day 9, and intertrial activity was increased simultaneously. In androgen-sterilized female rats, extinction was facilitated. HCG treatment of intact female rats delayed the extinction. The steroids used failed to affect the exploratory activity of castrated rats, indicating that, under the conditions tested, general activity and exploratory activity are not motivated by the same mechanism.     

Effect of septal damage on alcoholic motivation in the rat

Interconnection between predisposition to depressive-like state (DS) in stress situation and heightened addiction to ethanol was studied in nonlinear male white rats. Electrolytic lesion of the septum in animals inclined to the development of DS, led to a change from the passive type of reaction in stress conditions to the active type. The rate of formation of alcoholic motivation in these animals decreased in comparison with sham-operated rats. The effect of the septal lesion in rats with formed addiction to alcohol was less expressed. Conclusion is made that the passive type of reaction in extreme conditions is significant for the formation of alcohol motivation in rats, especially at early stages.     

Effects of D2 receptor agonist and antagonist on behavior of intact and ovariectomized rats

The involvement of D2 dopaminergic receptors in behavioral responses during ovary cycle was assessed in adult intact female rats and ovariectomized (OVX) female rats. Quinperole (0.1 mg/kg), D2 receptor agonist and sulpiride (10.0 mg/kg), D2 receptor antagonist were injected chronically to adult intact and ovariectomized (OVX) female rats either separately or in combination with 17beta-estradiol (0.5 microg) within 14 days. Behavior of these animals was assessed in the "open field" test, whereas passive avoidance performance served as a model of learning. In intact rats, the passive avoidance performance was observed only in metestrous and diestrous. Chronic quinperole administration to intact females resulted in the appearance of the passive avoidance performance in proestrous and estrous, as distinct from the control animals. The passive avoidance performance was not reproduced in OVX rats. Quinperole per se or in combination with 17beta-estradiol completely restored the passive avoidance performance in OVX rats. Moreover, quinperole or sulpiride administration to OVX rats increased horizontal locomotor activity, exploratory behavior, and grooming behavior.     

Differential effects of DGAVP on acquisition and extinction of active avoidance behavior

DGAVP facilitates consolidation and retrieval of active and passive avoidance behavior. In this study it was tested whether the long-term behavioral effects of DGAVP are the consequence of an initial increase in behavioral arousal during the learning phase. Animals that were preestimated in an open field test to be low active showed a lower number of conditioned avoidance responses (CAR's) during acquisition and extinction of a shuttle-box task than high active rats. DGAVP was administered 40 min prior to the 1st acquisition session. The immediate effect of DGAVP was a shift in the bell-shaped curve of the relation between arousal and performance (13); an increase in acquisition performance was observed with a low dose of DGAVP (0.1 microgram), while a decrease was found with a high dose of DGAVP (1 microgram). A dose-dependent inhibition of extinction was found in both low and high active animals. These results suggest an immediate effect of DGAVP on the rate of acquisition behavior, which may be a direct consequence of its arousing properties, and a long-term effect on extinction, indicating the formation of memory traces specific for vasopressin-related neuropeptides.     

Effects of cholecystokinin octapeptide sulphate ester and unsulphated cholecystokinin octapeptide on active avoidance behaviour in rats

The effects of peripherally administered cholecystokinin octapeptide sulphate ester and its unsulphated form on the active avoidance behaviour of rats were studied. The acquisition of avoidance behaviour was impaired, while extinction was facilitated, following cholecystokinin octapeptide sulphate ester or unsulphated cholecystokinin octapeptide treatment. These peptides had no action on open-field activity. It is concluded that peripherally administered cholecystokinin octapeptide influences acquisition and extinction of active avoidance behaviour and this effect is unrelated to general motor activity of the animals.     

Conditional Reflex Reaction of the Passive Avoidance in Female and Male Rats Exposed to Hypoxia at Different Terms of Prenatal Development

Elaboration of the conditional reflex reaction of passive avoidance was studied in the 42–46-day old offsprings of two groups of female rats: intact (control) and exposed to action of hypoxia at the 13th, 16th or 19th day of pregnancy. The parameter of learning was the time of stay of the rats in a dark camera, in which they obtained an electroshock. It is shown that the prenatal hypoxia has different effect on the ability to elaborate the conditional reflex reaction of passive avoidance in female and male rats. By this parameter, no differences were revealed in the male group between the control and the animals exposed to hypoxia at different terms of intrauterine development. In female exposed to hypoxia at the 19th day of gestation, it was not possible to elaborate the conditional reflex reaction of passive avoidance. In females exposed to hypoxia at the 13th day of gestation the parameters of learning were lower, whereas in the females exposed to hypoxia at the 16th gestation day they were higher than in control animals.     

Passive avoidance deficits following lesions of the posteroventral hippocampo-subiculo-entorhinal area in the developing rat

Young rats, 13, 16, and 20 days of age, underwent discrete bilateral electrolytic lesions of the posteroventral hippocampo-subiculo-entorhinal area, and were trained on a cool-draft-stimulus passive avoidance task 20 min later. Significant deficits in passive avoidance learning were observed at all ages studied following either small or more extended damage as compared to performance of sham-lesioned animals. The impairment was dependent upon the size of the lesion. Extended bilateral lesions of the parietal cortex overlying hippocampus induced no deficit. These results confirm that this part of the hippocampal complex plays a role in passive avoidance learning in the rat. They also show that this control of behavior is already established by the second week of life, thus supporting our previous experiments that demonstrate a cholinergic nicotinic involvement of this region in acquisition of passive avoidance as early as the 11th day of age.     

Prefrontal cortex aspiration in pups and juvenile rats: behavioural changes and recovery of function

Male Wistar rats sustaining prefrontal cortex aspiration or sham operation at 6 days or 30 days of age were submitted to the following behavioural tests: open-field, acquisition and retention of two-way active as well as passive avoidance tasks. In the open-field the locomotor activity proved enhanced in all the aspirated animals and this enhancement lasted for 30 days. In the two-day active avoidance task, an acquisition deficit was observed in both aspirated groups; but when retrained one month later, they were able to acquire the avoidance task like sham-operated rats and no difference appeared between the groups aspirated at 6 or at 30 days of age. Concerning the passive avoidance task, no difference could be detected between aspirated and sham-operated animals of both groups except that the rats aspirated at an early age (6 days) seemed to display a better avoidance ability in the retention test. These behavioural alterations (hyperactivity and impairment of the acquisition of the 2-way active avoidance) resulted from the prefrontal cortex aspiration, at whatever age this aspiration was performed (6 days or 30 days). They disappeared after a postoperative recovery period of about one month, as evidenced by this longitudinal study.     

大鼠脑发育不同时期学习记忆的变化及与NMDA受体通道动力 …

目的：研究大鼠脑发育不同时期学习记忆的变化及与ＮＭＤＡ受体通道动力学特性的关系。方法：采用学习记忆行为和离子通道动力学特性测定相结合的方法。结果：在爬杆主动回避反应中,发育早期大鼠习得和保持能力场明显强于成年大鼠。同时,发育早期大鼠训练后ＮＭ受体ｐＳ导电,而且３５ＰＳ通道开放时间和开放概率增加,３５ＰＳ通道长开放成份增多,有长ｃｌｕｓｔｅｒ开放而砀上大鼠２０Ｓ,３５ＰＳ通道关闭时间常数明显长于年龄     

Level of neuroactive steroids in the brain and sex-related peculiarities of formation and extinction of conditioned reflex in rats

Sex-related peculiarities of dynamics of brain sex steroids in the process of learning and extinction of the conditioned reflex of passive avoidance have been studied in model experiment. Prior to learning of the conditioned reflex, female rats were found to be distinguished by manifestation of anxiety and fear as compared with male rats. At formation of the conditioned reflex, no significant sex-related differences were detected between males and females, whereas extinction of the conditioned reaction of passive avoidance in males occurred by 2–3 days faster than in females. At learning of conditioned reaction of passive avoidance, in sexually mature male rats there was revealed an increase of the testosterone content in various brain structures, especially in hippocampus and frontal cortex, while its level in blood plasma remained unchanged. Also shown was an elevation of estradiol concentration in female amygdale, whereas at extinction of the conditioned reaction of passive avoidance, a rise of estradiol values was noted in hippocampus and cingular cortex. At the same time, the testosterone level in blood plasma did not change, whereas after extinction of the conditioned reflex the estradiol concentration decreased statistically significantly. Different dynamics of changes of the sex steroid levels in brain and blood plasma can indicate a possibility of their formation in the nervous tissue. The performed correlation analysis confirms the concept of selective involvement of testosterone and estradiol of individual brain structures in realization of processes of learning and memory in sexually mature male and female rats.     

海马内生长抑素与γ－氨基丁酸在大鼠穿梭箱主动回避反应中的作用

本实验以大鼠穿梭箱主动回避反应（ＡＡＲ）的习得和消退为学习记忆的指标,研究了海马内生长抑素（ＳＳ）和γ－氨基丁酸（ＧＡＢＡ）在学习记忆中的作用。结果如下：（１）经训练而建立了ＡＡＲ的大鼠,其海马内ＳＳ较对照组显著增高,而海马内ＧＡＢＡ含量却明显降低;（２）海马内注入ＳＳ的耗竭剂半胱胺（Ｃｙｓ,２０ｇ／Ｌ）使大鼠ＡＡＲ的习得受到明显损害,ＡＡＲ的消退显著加速,海马内ＳＳ明显降低,而ＧＡＢＡ含量却显著升高;（３）海马内注入ＧＡＢＡ（２００ｇ／Ｌ）使大鼠ＡＡＲ的消退显著加速的同时,其海马内ＳＳ含量亦显著降低。由此表明,海马内ＳＳ可能有促进学习记忆的作用,而海马内ＧＡＢＡ升高则有相反的效应;二者在海马调控学习记忆过程中具有重要作用。     

Extinction of passive avoidance response in various mouse strains

Dependence of the passive avoidance extinction dynamics on a mouse strain was shown. Mice C57BL/6J and AKR/J extinguished more quickly relative to DBA/2J, CBA/Lac and BALB/c, and this extinction was stable. Individual instability of extinction was characteristic of C3H/HeJ mice. Extinction of the passive avoidance in mice CBA/Lac and BALB/c was slower: with a delay in the beginning and prolonged retention of memory trace of the shock exposure. In DBA/2J mice, the extinction was impaired. These data suggest that DBA/2J, CBA/Lac and BALB/c mice constitute groups of risk with high predisposition to impairment of extinction of memory of aversive events, which is thought to be a symptom of a depressive-like state.     

Neonatal androgen levels and avoidance learning in prepubescent and adult male rats

Neonatal male rats were injected with 1.25 mg of testosterone propionate (TP) and compared with oil-injected controls on the acquisition of an active and passive avoidance response at 25 days of age. The TP treated animals acquired the active avoidance response significantly faster than controls, but no differences were found between groups tested on the step-down passive avoidance task. The active-avoidance paradigm was repeated at 70 days of age, with experimental and control animals receiving the same neonatal treatment as the prepubescent subjects. Again the TP group showed facilitated acquisition of the active avoidance response. The TP treatment also produced an increase in activity levels and aversion threshold to footshock in the prepubescent animals. Therefore the active avoidance effect may be interpreted more parsimoniously as a reflection of these latter effects, rather than learning per se.     

Plasma uptake and in vivo metabolism of [Leu]enkephalin following its intraperitoneal administration to rats

To understand better how [Leu]enkephalin (LE) acts to modulate learning and memory in rats, the plasma uptake, disappearance, and metabolism of LE were investigated following its intraperitoneal administration. Concentrations of [3H]-LE and its radioactive metabolites were determined by thin layer chromatography in plasma samples withdrawn from rats at various times after injection of peptide. As measured in rats receiving an IP injection of a dose of LE (3 micrograms/kg) that impairs active avoidance conditioning, the LE was very rapidly metabolized, with greater than 95% of plasma [3H] in the form of metabolites by 1 min after injection. Despite this rapid metabolism, low but measurable quantities of intact LE were detectable in plasma at all sampling times. Consistent with a greater potency of D-Ala2-[D-Leu5]enkephalin (DADLE) than of LE in modulating avoidance conditioning, DADLE was less rapidly metabolized than was LE following its IP administration. The metabolism of DADLE and LE in vivo was more rapid than it was in plasma in vitro, suggesting a role for membrane bound enzymes in the metabolism of IP-administered enkephalins. The data demonstrate that, despite a rapid hydrolysis of LE in vivo, sufficient LE is present in plasma following IP administration of a behaviorally active dose to support a role of circulating intact LE in the modulation of avoidance conditioning.