Influence of intracerebral administration of NO agents in dorsal hippocampus (CA1) on cannabinoid state-dependent memory in the step-down passive avoidance test

In the present study, the effects of nitric oxide agents on WIN55, 212-2 induced state-dependent memory of passive avoidance task were examined in mice. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice. Post-training intra-CA1 administration of CB1 and CB2 receptor agonists, WIN55, 212-2 (0.25, 0.5 and 1 µg/mouse), dose-dependently decreased memory retrieval. The memory impairment induced by post-training administration of WIN55, 212-2 (1 µg/mouse) was restored by pre-test administration of the same dose of the drug (1 μg/mouse, intra-CA1), showing the WIN55, 212-2 state-dependent memory. Single intra-CA1 administration of l-arginine (0.3, 1 and 3 µg/mouse) or L-NAME (0.3, 1 and 3 µg/mouse), 5 min pre-test could not alter memory retrieval. On the other hand, in the animals in which retrieval was impaired due to post-training administration of WIN55, 212-2 (1 µg/mouse), pre-test intra-CA1 administration of l-arginine (1 and 3 µg/mouse), but not L-NAME (0.3, 1 and 3 µg/mouse) 24 h after training restored memory retrieval. Also, in the animals which received both post-training (1 µg/mouse) and pre-test injections of WIN55, 212-2 (1 µg/mouse), the injection of L-NAME (3 µg/mouse, intra-CA1), 2 min before pre-test administration decreased retrieval. Furthermore, in the animals under the influence of post-training administration of WIN55, 212-2 (1 µg/mouse), pre-test co-administration of non-effective doses of WIN55, 212-2 (0.25 µg/mouse) and l-arginine (0.3 and 1 µg/mouse), increased the restoration of memory by pre-test WIN55, 212-2. These findings may demonstrate the involvement of NO in state-dependent memory induced by intra-CA1 administration of WIN55, 212-2.     

Influence of cholinergic system modulators on morphine state-dependent memory of passive avoidance in mice

Memories are shown to be impaired in mice during step-down passive avoidance tasks with substantial residual effects lasting as long as 24 h after the pre-training administration of morphine. Administration of the same dose of morphine as a pre-test treatment restored memory. Since the cholinergic system has been reported to be involved in several actions of morphine, e.g.: modulation of memory and analgesia, we have investigated the part played by cholinergic modulator drugs, on the memory recall in mice. The locomotor activity of animals was studied as well. Administration of either atropine, a peripheral-central muscarinic antagonist, or mecamylamine, a peripheral-central nicotinic antagonist, failed to alter memory themselves, but significantly prevented morphine-induced memory recall following co-administration with morphine. Neither hexamethonium, a peripheral nicotinic antagonist, nor neostigmine, a peripheral anticholinesterase, showed intrinsic activity or a significant change in morphine-induced memory recall. Finally, physostigmine, a peripheral-central anticholinesterase, not only induced memory recall itself, but also increased morphine-induced retrieval. Memory recall of the step-down passive avoidance task following drug combinations was not related to locomotor activity changes. Thus, morphine-induced memory recall appears to be influenced by central cholinergic activity.     

Effects of amygdaloid lesions on the performance of rats in four passive avoidance tasks

The effects of amygdaloid lesions on shock punished step-down and rearing responses, quinine punished drinking, and ice water punished step-through responses were investigated in 4 experiments. Amygdaloid lesions impaired the suppression of step-down, rearing, and step-through responses but had no effect on the suppression of quinine consumption. Various interpretations of the response disinhibitory effects of amygdaloid damage are considered. It is concluded that no unitary explanation adequately explains this phenomenon. More extensive investigations of the conditions producing response disinhibition and their anatomical organization are suggested.     

Effects of retention interval and gonadectomy on sex differences in passive avoidance behavior

Female rats show more response suppression in aversively motivated learning when the effect of presentation of an aversive stimulus upon subsequent responding is measured immediately, whereas males show more suppression in procedures in which the effect of an aversive stimulus is measured after longer intervals. To test whether this divergence can indeed be attributed to temporal parameters, step through passive avoidance was studied using various intervals between shock and retention trial. In contrast to the hypothesis, males showed more response suppression than females when tested directly after shock presentation. This sex difference was also observed at longer intervals. The highest levels of passive avoidance was observed at a 15 minute interval in all groups. Ovariectomy had no effect on the performance of females, but castration of males significantly decreased their performance. These findings demonstrate that the presence of testosterone in adulthood is critical for the masculine pattern of this behavior.     

NMDA receptors are involved in Ginkgo extract-induced facilitation on memory retention of passive avoidance learning in rats

Herbal therapies are commonly used to enhance memory and learning. Ginkgo biloba has shown to be one of the most popular herbs that is used to treat amnesia and retard age related memory deficits. Although, there have been several reports on the memory enhancing effects of Ginkgo, involvement of glutamatergic system that plays pivotal role in learning and memory has not been precisely assessed so far. The current study intended to investigate the effect of Ginkgo intake on amnesia while NMDA (N-methyl D-aspartic acid) receptors blocked by the administration of MK-801. The study used passive avoidance (PA) task to investigate the effect of chronic administration of Ginkgo extract (40 and 90 mg/kg; oral) on the memory span in male Wistar rats, suffering from MK-801-induced forgetfulness (0.06 and 0.1 mg/kg; i.p.). The results indicate that Ginkgo was able to remove MK-801-induced forgetfulness, indicating that Ginkgo can affect memory retention but not effect on passive avoidance acquisition, using pathways other than glutamatergic system as well. The results might indicate that Ginkgo extract can be effective in removing forgetfulness caused by inhibiting NMDA receptors from performing their activities.     

Fear behavior and passive avoidance deficits in mice with amygdala lesions

Mice with lateral amygdala lesions showed a deficit in passive avoidance behavior during a 10-min test of shock-contingent activity. Although these mice received more shocks than controls they displayed little or no evidence of fear behavior and continued to make punished responses throughout the test period. These results, together with those of previous studies, suggest that the impairment in shock motivated behavior in animals with amygdala lesions is due to a decrement in fear arousal.     

Age effects on passive avoidance behavior of vasopressin-deficient Brattleboros

Experiments in which vasopressin-deficient Brattleboros were tested in a passive avoidance procedure have yielded contradictory results. Some investigators observed the passive avoidance behavior of these subjects to be inferior to that of normal controls, while others failed to observe such differences. Inspection of the literature suggested that age differences between subjects which participated in these experiments might be responsible for the discrepancy. In the present experiment, HO-DI and HE Brattleboro rats of different ages were tested in the standard passive avoidance task. Passive avoidance performance of HO-DIs was, indeed, influenced by the age of the subject at the time of testing; HO-DIs reentered the shock compartment sooner than HE at 35 days, but later than HE at 120 days. There was no difference between the two groups of subjects at 60 days. The percentage of HO-DIs which reentered the shock compartment on the post-shock trial decreased with increasing age.     

Deficits in passive avoidance and fear behavior following bilateral and unilateral amygdala lesions in mice

Bilateral amygdala lesions severely disrupt passive avoidance and fear behaviors. The effects of unilateral amygdala lesions on these behaviors are unclear, though unilateral lesions in other structures produce deficits similar to those produced by bilateral lesions. In the present experiment, female mice with unilateral or bilateral amygdala lesions manifested similar patterns of passive avoidance and fear behavior deficits. The results are discussed in light of previous passive avoidance and unilateral lesion studies.     

Passive avoidance and carbachol excitation of the caudate nucleus

Post-trial injections of carbachol into the caudate-putamen complex of rats impaired single-trial passive avoidance learning. Control placements of carbachol in the lateral hypothalamic region did not. Such injections did not alter ECoG activity of the frontal cortex. Larger dosages caused seizures and recurrent spindling similar to that effected by suprathreshold electrical stimulation. The results are discussed with regard to possible involvement of extra-caudatal influences.     

Open-field behavior, habituation and passive avoidance learning: Effect of ACTH and hydrocortisone on Normal and adrenalectomized rats

Exploratory behavior (GMA) and habituation rate (IH) were studied in an open-field situation in normal and adrenalectomized rats. Following this procedure the rats were subjected to passive avoidance learning (PA). Wide-spreading individual differences were observed in the exploratory behavior and the tendency of habituation of normal rats. As compared to the normal values, either the adrenalectomy which was performed 24 hr, 7 days and 28 days prior to the experiments or the ACTH and hydrocortisone treatment failed to modify the GMA and the IH significantly. An improvement of PA was found in the normal rats following ACTH and hydrocortisone treatment. In the adrenalectomized animals the hydrocortisone proved to be effective, whereas ACTH did not influence PA. No correlation was found between GMA, IH versus PA values and the influence of ACTH and hydrocortisone administration on these parameters. It is concluded that the direction of PA is unpredictable on the basis of the open-field test performed on R-Amsterdam strain of rats, and the effect of ACTH on passive avoidance learning is mediated through the adrenal glands.     

The effect of iron deficiency during development on passive avoidance learning in the adult rat

Offspring of iron-deprived and normal female Long Evans rats were placed on either iron deficient or a normal diet from weaning to 115 days. At 100 days of age, they were trained on a single trial passive avoidance shuttlebox task. At 115 days of age they were sacrificed for measures of liver and brain non-haem iron, and haemoglobin concentrations. Brain iron levels were shown to be affected more by maternal iron diet than postweaning iron diet. The reverse was true for liver iron and haemoglobin, while bodyweight was dependent only on maternal diet. At the behavioural level, no effects were observed on number of trials to extinction. However, maternally deprived offspring showed significantly shorter escape latency on the learning trial and fewer false entries on extinction trials, with postweaning diet exerting no effect on these behaviours. The behavioural results may be interpreted in terms of increased sensitivity to noxious stimuli in maternally deprived rats. No simple explanation for the iron status results is apparent.     

Effects of hippocampal lesions on passive avoidance and taste aversion conditioning

Rats with electrolytic lesions of the posteroventral hippocampus failed to perform a simple passive avoidance of footshock but showed conditioned aversion to a saccharin solution paired with apomorphine induced gastrointestinal distress. On the other hand, anterodorsal hippocampal lesions interfered with performance on both tasks. The more general deficit produced by the dorsal lesions is attributed to the fact that such lesions extended into the fimbria, and thus destroyed outputs from a larger area of the hippocampus.     

Opposite action of oxytocin to vasopressin in passive avoidance behavior in rats

The effect of oxytocin and lysine-8-vasopressin on step-down passive avoidance behavior has been studied in rats. Step-down latency was considerably shortened after treatment with oxytocin and lengthened by vasopressin. The data suggest an opposite action of oxytocin to vasopressin on step-down latency.     

Sexual dimorphism in passive avoidance behavior of rats: Relation to body weight,age, shock intensity and retention interval

Female rats were inferior to age- and weight-matched males in the retention of a step-through type passive avoidance response 24 and 48 hr after the learning. This sex difference could be observed at different intensities of foot shock which was used as aversive stimulus during the single learning trial. Additionally, unlike in males, retention of the passive avoidance response in the females was not the function of shock intensity. Male and female rats, however, showed similar passive avoidance if tested immediately after the learning trial. The results suggest the existence of sexual dimorphism in memory processes.     

Cue-induced recall of a passive avoidance response by rats with hippocampal lesions

Two experiments are reported in which a stimulus reminder technique was used in an attempt to compensate for the disruptive effects of hippocampal lesions on passive avoidance (PA) conditioning. Groups of hippocampal, cortical and operated control rats were trained to run down an alley for water reward. When the approach response had stabilized, shock was introduced in the goal-box, resulting in increased running times in the control groups and the characteristic PA impairment in the hippocampal group. A recall test was administered 24 hr later but 2 hr before the test, animals were reminded of the previous treatment by being exposed to: (1) shock and related stimuli, (2) related stimuli only, or (3) neutral stimuli. The PA performance of the hippocampus groups in the recall test improved to the level of controls following conditions 1 or 2; there was no effect of condition on Treatment 3. Performance of control groups was virtually unaffected by any of the reminder conditions. The similarities were noted between these results and those of partial cueing studies involving human amnesics with known or suspected damage to the hippocampal system.     

Effects of olfactory bulb removal on fear responses and passive avoidance in the rat

Following complete bulbectomies, male hooded rats showed an increase in irritability and difficulty of handling, but a decrease in timidity or fear responses. After rats had learned to drink in an open field, a cat was confined in the center, and fear was defined by the behavior of controls, viz., almost total suppression of drinking and long periods of freezing, broken by brief bursts of high-speed activity. Bulb animals could not have differed more radically. Bulbs showed neither freezing nor suppression of drinking. The present results could not be attributed to differences in shock reactivity; nor could they be attributed to differences in learning or retention. Bulb animals also showed an impairment on the acquisition of step-down passive avoidance but no difference in step-downs after acquisition. These results argue against an impairment of response inhibition. The present study suggests that bulbectomy increases irritability and decreases timidity.     

Prolonged ethanol consumption influences shuttle box and passive avoidance performance in rats

Rats were chronically maintained on an ethanol liquid diet for 16 days. Three weeks after cessation of ethanol intake, animals were tested for the acquisition of shuttle box avoidance and the retention of passive avoidance behaviour. Alcohol consuming rats showed a significant impairment of acquisition in the shuttle box task, and a slight impairment in the retention of the passive avoidance response. It is concluded that ethanol or its metabolites can induce long-term effects on learning and memory processes, even after cessation of drug consumption.     

Combined effects of ECS and Metrazol on passive avoidance learning

The combined effects of a non-convulsant dosage (10 mg/kg of body weight) of Metrazol and 60 min ECS were investigated in order to find out if the interaction of the two would produce an amnesic effect upon passive avoidance learning. The main group of rats was given FS, with an immediate posttrial injection of Metrazol, followed by ECS at 60 min. Four other groups were given footshock (FS) followed by saline injection. Three of these 4 groups received ECS following FS at 30, 45, and 60 min respectively, leaving one group receiving only footshock. The footshock only and 60 min ECS groups had the same mean starting and running times, indicating no amnesia with 60 min ECS. The Metrazol 60 min ECS group had a significant retention deficit, falling between the 45 and 30 min groups. The results support the consolidation disruption hypothesis of ECS induced amnesia, and are contrary to the incubation interpretation of these effects.     

Effects of additional cues on passive avoidance learning and extinction in rats with hippocampal lesions

Following the acquisition of a water-rewarded approach response in a straight runway, the effects of introducing shock in the goal box (passive avoidance - PA) or withdrawing reinforcement (extinction) were compared in hippocampal, cortical, and operated control groups of rats. Under standard test conditions, hippocampal groups were impaired in PA learning and showed strong resistance to extinction, relative to the control groups. When additional cues were provided such that external stimuli associated with goal box events could be easily detected early in the runway, performance differences between the hippocampal and control groups were eliminated in the PA test and significantly reduced in extinction. The results emphasize the inefficient processing by hippocampally-damaged animals of stimulus cues following a shift in experimental contingencies.     

Brief communication ventromedial hypothalamus: fear conditioning and passive avoidance in rats.

Lesions in the ventromedial hypothalamus are found to induce deficient fear acquisition in rats. This deficit parsimoniously explains a secondary, i.e. passive avoidance, deficit and predicts other behavioral disturbances.