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PubMed1990

Nootropic effects of ACE inhibitors in mice.

The angiotensin converting enzyme (ACE) inhibitors captopril and enalapril and the nootropic piracetam reduced the amnesiogenic effects of cerebral electroshock treatment in mice. These compounds also directly improved passive-avoidance learning if administered before the learning trial. When given immediately after the learning trial, captopril and piracetam were active, but not enalapril. Captopril, but neither enalapril nor piracetam, facilitated memory retrieval after a 2-month retention interval. Unlike those of piracetam, the memory-improving effects of captopril and enalapril are not established by aldosterone-receptor blockade, suggesting that the two types of drug act via different mechanisms of action.

Adrenalectomy↗

PubMed1981

Effects of chronic alcohol feeding on thiamin status: biochemical and neurological correlates.

The effects of chronic alcohol feeding on thiamin status are controversial; both adverse and beneficial effects have been reported. In order to study these effects, rats and baboons were pair-fed liquid diets containing thiamin in excess of dietary requirements and either ethanol (rats 36%, baboons 50% of total calories) or the identical diet with ethanol substituted isocalorically by carbohydrate. In the rat, chronic alcohol feeding for up to 6 months had no effects on tissue thiamin measured by transketolase assay, thiamin pyrophosphate effect, or bioassay with Ochromonas danica. Shuttle box avoidance learning in rats was impaired in animals rendered thiamin deficient but not in animals fed control or alcohol-containing liquid diets. In baboons, chronic alcohol feeding for up to 3 yr had no effects on blood levels of thiamin or on urinary excretion of thiamin. Thus, chronic alcohol feeding along with nutritionally supplemented diets does not appear to significantly affect thiamin status.

Animals↗

PubMed1992

Halothane anesthesia causes state-dependent retrieval failure in mice.

Effects of exposure to halothane on memory processing was studied using single-trial inhibitory avoidance learning to measure retention. Mice were anesthetized with halothane either before training, immediately after training, or both before training and before testing. Results showed that memory was not impaired by posttraining halothane exposure, indicating that the anesthetic does not cause retrograde amnesia. Mice trained after recovery from halothane showed a robust memory loss 24 h later. This deficit could be alleviated by reexposure to the anesthetic before the retention test. Mice given multiple training trials following recovery from the anesthetic showed a normal rate of learning when compared with controls, but deficient retention. This indicates that the performance deficit was the result of impaired retention (anterograde amnesia) rather than disrupted acquisition. Anterograde amnesia occurred when training was delayed up to 2 h after recovery from anesthesia. These findings indicate that the memory impairment following halothane anesthesia is the result of a state-dependent retrieval failure.

Amnesia, Retrograde↗

PubMed2004

Reversible lesion of the rat's orbitofrontal cortex interferes with hippocampus-dependent spatial memory.

In this study, tetrodotoxin (TTX) inactivation was employed to evaluate the involvement of the rat's orbitofrontal cortex (OFC) in hippocampus-dependent spatial memory using Morris water maze (MWM) and place avoidance learning (PAL) tasks. In Experiment 1, rats trained in MWM task with two blocks of four trials per day for 3 consecutive days received bilateral injections of either TTX or saline into the OFC 60 min before each daily training session. The acquisition of spatial memory was evaluated 24h after the last training day and it was shown an impairment by the TTX. In Experiment 2, bilateral intra-OFC injections of TTX or saline were made immediately after two blocks of four trials. Testing 24h later, it was revealed that TTX also impairs spatial memory consolidation. In Experiments 3 and 4, rats were trained in a single 30-min session to avoid a 60 degrees segment of the stable circular (80-cm diameter) arena, entering which was punished by a mild shock (PAL task) and retention was tested 24h later in a 30-min extinction session. Bilateral injections of TTX or saline were made into the OFC 60 min before training or immediately after training. Again, TTX impaired the place avoidance retention when it was injected into the OFC either before (acquisition phase) or after (consolidation phase) training. These findings indicate that functional integrity of the OFC is necessary for both the acquisition and the consolidation of hippocampus-dependent spatial memory in rats.

Anesthetics, Local↗

PubMed2001

Evidence that age-induced decline in memory retention is delayed in growth hormone resistant GH-R-KO (Laron) mice.

Although the role of growth hormone (GH) in aging is controversial, the recent production of GH-R-KO mice may provide a means for elucidating its importance. Using the inhibitory avoidance learning task as a measure of cognitive aging, the present study compared learning and retention in young and old GH-R-KO mice and their normal siblings. Results for the old normal animals agreed with the current literature, in that the ability of old animals to retain learned information declined over time. However, retention in the old GH-R-KO mice did not decline between the 24-h, 7-day and 28-day retention tests and did not differ from young animals. To determine whether performance differences seen in the old normal vs. old GH-R-KO groups were due to locomotor behavior or emotionality, both groups were tested in the elevated-plus maze. Results showed that the normal and GH-R-KO mice did not differ in number of open or closed arms entered, time spent in closed or open arms or time taken to first enter an open arm. Thus, it was concluded that inhibitory avoidance performance was not affected by differences of locomotor activity or emotionality, and that the absence of GH signaling may be associated with improved long-term memory in aging mice.

Aging↗

PubMed1983

Passive avoidance training increases fucokinase activity in right forebrain base of day-old chicks.

Fucokinase (EC 2.7.1.52) activity was estimated in supernatants of homogenate from day-old chick forebrain. Enzyme kinetic studies gave a Km of 4.5 X 10(-6) M and Vmax of 3.72 nmol fucose converted into fucose-1-phosphate/mg prot/h. The pH optimum was 7.5. The enzyme is thus considerably more active than was reported for other species and tissues. There were no differences in enzyme activity between the four forebrain regions studied. One hour after chicks were trained on a one-trial passive avoidance learning paradigm, enzyme activity in the right forebrain base increased 14% over control values (p less than 0.02). The 11.3% increase in activity in the left forebrain base and 10.3% increase in the left roof were not statistically significant. The relationship of this change to the increased fucose incorporation into glycoproteins known to occur over a similar time period and the significance of the lateralization of the increase are discussed.

Animals↗

PubMed1991

Are rats with genetic absence epilepsy behaviorally impaired?

Absence seizures in humans are characterized by unresponsiveness to external stimuli and inactivity. However, in typical generalized non-convulsive epilepsy in children, intellectual capacities are considered to be normal. Wistar rats from an inbred strain with spontaneous absence-like seizures were compared with rats from the outbred control strain in various behavioral tasks in order to detect possible impairments related either to the absence epilepsy or to occurrence of spike and wave discharges (SWD). Spontaneous circadian locomotion, exploratory activity in an open field, social interactions with an unfamiliar conspecific and mouse killing behavior were similar in both strains. Avoidance learning in a shuttle box or food reinforced learning in a Skinner test were unimpaired or even improved in epileptic rats. During performance of a learned task either in the Skinner box or in a conditioned sound-bar pressing task, SWD were suppressed in epileptic rats as long as they were working for reinforcement. SWD reappeared when the motivation to perform the task had declined: unresponsiveness to a conditioned stimulus was then observed during SWD. These data are in agreement with observations commonly described in children with typical genetic absence epilepsy.

Aggression↗

PubMedDate not supplied

[Non-classic effects of luliberin confirming the pleiotropy of neuropeptides].

The effects of synthetic neuropeptide LH-RH and its analogues were studied in experiments on 174 white male rats. The influence of the substances was shown on instrumental avoidance learning in Y-shaped maze. Convulsive and anticonvulsive effects of the preparations were studied on experimental model of corasol seizures. The analgetic effect of the substances was evaluated by behavioural pain reaction to electrical stimulation of the tail root. Analgetic, anticonvulsive, and psychostimulating LH-RH properties confirm polyfunctionality and "pleiotropy" of neuropeptides as a class of new endogenous informational compounds.

Analgesics↗

PubMed1988

[Pharmacological correction of experimental alcoholic embryopathy].

In the experiments on the progeny of ethanol-exposed rats it was shown that consumption of 15% alcohol instead of water during pregnancy resulted in the worsening of shuttlebox avoidance learning and decrease in succinate dehydrogenase activity in the visual and sensorimotor cortex. These data are indicative of cerebral hypoxia during embryogenesis. The injection of synthetic opioid peptide dalargin during critical periods of development (at the end of embryogenesis and early ontogeny) prevented partially the disturbances of higher nervous activity and tissue breathing which were induced by alcohol intoxication. Possible mechanisms of positive dalargin effect are discussed.

Animals↗

PubMed2003

Altered long-term corticostriatal synaptic plasticity in transgenic mice overexpressing human CU/ZN superoxide dismutase (GLY(93)-->ALA) mutation.

Apart from the extensive loss of motor neurons, degeneration of midbrain dopaminergic cells has been described in both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Mice overexpressing the mutant human Cu/Zn superoxide dismutase (SOD1) show an ALS-like phenotype in that they show a progressive death of motor neurons accompanied by degeneration of dopaminergic cells. To describe the functional alterations specifically associated with this dopaminergic dysfunction, we have investigated the corticostriatal synaptic plasticity in mice overexpressing the human SOD1 (SOD1+) and the mutated (Gly(93)-->Ala) form (G93A+) of the same enzyme. We show that repetitive stimulation of the corticostriatal pathway generates long-term depression (LTD) in SOD1+ mice and in control (G93A-/SOD1-) animals, whereas in G93A+ mice the same stimulation generates an N-methyl-D-aspartic acid receptor-dependent long-term potentiation. No significant alterations were found in the intrinsic membrane properties of striatal medium spiny neurons and basal corticostriatal synaptic transmission of G93A+ mice. Bath perfusion of dopamine or the D(2) dopamine receptor agonist quinpirole restored LTD in G93A+ mice. Consistent with these in vitro results, habituation of locomotor activity and striatal-dependent active avoidance learning were impaired in G93A+ mice. Thus, degeneration of dopaminergic neurons in the substantia nigra of G93A+ mice causes substantial modifications in striatal synaptic plasticity and related behaviors, and may be a cellular substrate of the extrapyramidal motor and cognitive disorders observed in familial and sporadic ALS.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1981

Behavioural effects of etiracetam in rats.

The effects of etiracetam, a structural analogue of piracetam, were investigated in rats on Y-maze discrimination acquisition, on open field behaviour, on one-trial passive avoidance learning and on shuttlebox acquisition and extinction. The results indicate that this drug significantly enhances acquisition and may improve retention without having any detectable effects on spontaneous behaviour, not even in very high doses (500 mg/kg IP). Sensitivity to footshock, measured as "flinch" thresholds, was not altered by etiracetam in doses of 25 or 100 mg/kg IP. For a shuttlebox task the effective dose-range lies between 20--30 mg/kg IP, provided pretreatment during 4 days is given. Without pretreatment, i.e. when the drug is only administered during the relatively fast acquisition in the shuttlebox, it was found that acquisition was not enhanced, but extinction of the acquired behaviour was significantly inhibited. The effects of etiracetam can be found at lower dose-levels than with piracetam and also in tests (passive avoidance, shuttlebox) in which piracetam has no or only marginal effects.

Animals↗

PubMed1990

Strain-dependent differences in hippocampal glucocorticoid binding capacity and active avoidance in the mouse.

Maximal individual [3H]corticosterone binding capacity in the hippocampus was lower in C57BL/6 mice than in BALB/c mice, and positively correlated with active avoidance learning in the two strains. Moreover, a parallel difference in the activity of hypothalamo-pituitary adrenocortical axis (HPAA) was found, consisting in a level of plasma corticosterone in C57BL/6 higher than in BALB/c mice. These results confirm the genetically determined differences in behavior of C57BL/6 and BALB/c mice, and demonstrate their association with differences in hippocampal corticosterone binding capacity, pointing to a functional relationship between the behavioral and neuroendocrine parameters.

Animals↗

PubMed2004

Acute and long-term consequences of single MDMA administration in relation to individual anxiety levels in the rat.

Our previous work has shown that normal male Wistar rats can differ systematically in their behavioral response to the elevated plus-maze (EPM), where animals with high (HA) or low anxiety (LA) levels can be identified based on the percentage of time spent in the open arms. These animals also differ in other behavioral tests (e.g. active avoidance), and in their serotonin levels in the ventral striatum. Here, we tested whether such HA and LA rats might respond differently to the amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). This drug can affect psychomotor activation and anxiety; effects which are probably due to its pronounced serotonergic and dopaminergic impacts in the rat brain. Based on a routine screening procedure in the plus-maze, male Wistar rats were divided into HA and LA sub-groups, in which rectal temperature was measured. Thirty minutes after the i.p. injection of MDMA (7.5 or 15 mg/kg) or vehicle, they were again tested in the plus-maze. During the next 3 weeks, the animals underwent further behavioral tests (plus-maze, open field, active avoidance, forced swimming) to test for possible long-term consequences of MDMA. Rectal temperature was found to be higher in LA than HA rats and was especially increased with the higher dose of MDMA (15 mg/kg). In the acute plus-maze test, the lower dose of MDMA led to an anxiogenic-like profile, whereas the higher dose led to an anxiolytic-like profile, both in HA and LA rats. Possible long-term consequences of MDMA were only tested with 7.5 mg/kg MDMA, since the 15 mg/kg dose led to a high level of lethality. The analysis of open field, plus-maze (performed after 9-12 days), and forced swimming behavior (performed after 20-21 days) did not provide indications for lasting effects of MDMA. In contrast, active avoidance learning was impaired in LA- but not HA-rats treated with MDMA. A single injection of MDMA does not only have acute effects on anxiety and psychomotor activation, but can also have some prolonged or delayed task-dependent behavioral consequences. The detection of such sequels can require that individual differences are taken into account and here, determining anxiety levels in the EPM seems to serve as a useful approach.

Analysis of Variance↗

PubMed1988

The propensity for schedule-induced polydipsia is related to differences in conditioned avoidance behaviour and in defense reactions in a defeat test.

In line with previous research showing that animals predisposed to develop schedule-induced polydipsia when submitted to intermittent distribution of food show differential behavioural and neurochemical characteristics, the present experiments investigated the nature of defense reactions to aversive situations in rats that do or do not develop schedule-induced polydipsia. It was found that rats that engage in excessive drinking during intermittent feeding display more rapid active avoidance learning in a 2-way shuttle-box and show less freezing when confronted with an aggressive resident male in a defeat test than those that do not develop schedule-induced polydipsia. These results are consistent with the hypothesis that individual differences in the propensity to exhibit oral consummatory activities in conditions of mild stress are related to the ability to shift behavioural programmes in response to external stimulation.

Aggression↗

PubMed1994

Age-related memory decline and longevity under treatment with selegiline.

The MAO-B inhibitor selegiline is used in the treatment of Parkinson's disease. Further, beneficial effects in Alzheimer's disease have also been described as well as neuroprotective effects, increased longevity and an attenuation of age-related cognitive decline in experiments using rats. Our studies in mice and Syrian hamsters aim at the question whether the effects of selegiline reported in the rat can be generalized to other species. Aged female NMRI-mice (23 mo.) treated with selegiline (0.25 mg/kg, i.p., 3 times a week for 2-3 weeks) showed no treatment effect in the Morris water maze and in passive avoidance learning after 2 and 3 weeks of treatment. However, Syrian hamsters chronically treated with selegiline (0.05 mg/kg/day in the food, starting at 12 months old) showed a 3 month delay in the age-related decline of spontaneous alteration behavior, a measure of longer-term memory, compared to untreated controls. Since treated hamsters also show increased longevity (study still in progress) the data suggest a protective effect of a chronic treatment with selegiline against age-related cognitive and physical decline.

Aging↗

PubMedDate not supplied

Reversal of ECS-induced amnesia by post-ECS injections of amphetamine.

Water deprived rats were trained to drink from a water spout within an apparatus on each of 2 days. On the third day, passive avoidance of the spout was induced by giving the animal a 0.3 sec, 5 mA footshock after 1 lick at the spout. A test for retention of the avoidance learning was given 48 hr following training. ECS administered through cortical electrodes at 15 sec following the footshcok impaired retention. The amnesia was attenuated when amphetamine (1 mg/kg) was injected immediately but not at 6 hr following the ECS. In a second experiment, attentuation of amnesia by amphetamine was not found when the ECS occured at 4 sec instead of 15 sec following the footshock. The results are interpreted in terms of reactivation by amphetamine of a consolidation process that was interrupted by ECS.

Amnesia↗

PubMed1976

Differential effect of morphine on trigeminal nucleus versus reticular aversive stimulation: independence of negative effects from stimulation parameters.

Electrodes were implanted in mesencephalic, pontine, and bulbar reticular formation, and in spinal trigeminal nucleus and tract of rats. Central and peripheral aversive response thresholds were studied under normal conditions and with morphine. Peripherally elicited aversive reactions were assessed with tail-flick, hot-plate, and footshock responses. Centrally elicited aversive reaction thresholds were in all cases based on unconditioned behavioral distress signs (non-stereotyped, escape-like movements, vocalization, freezing, excretion, etc.) and confirmed in some cases with avoidance learning. Morphine (10 mg/kg) elevated the unconditioned aversive reaction threshold for brain stimulation in the trigeminal complex and for peripheral aversive stimulation, but failed to affect the thresholds for reticular brain stimulation. The failure to affect reticular thresholds was independent of stimulation frequency. Thresholds for 5 and 200 Hz sinusoidal stimulation were both unaffected as were previously reported thresholds with 333 Hz pulsatile stimulation. Trigeminal nucleus and tract stimulation were affected in similar degrees. The data were discussed as supporting descending inhibitory models of opiate analgesia.

Analgesia↗

PubMed1992

Evaluation of prenatal aldrin intoxication in rats.

The aim of the present study was to evaluate the impact of prenatal exposure to low doses of aldrin on physical and behavioral developments of rats (1-21 days old). To detect the possible persistent adversities produced by this exposure, the animals were also tested when adults (90 days old). Plasma determinations of both aldrin and its metabolite dieldrin and histopathological evaluations of brain slices were also performed in adult animals. Pregnant female rats were subcutaneously (s.c.) treated with aldrin (1.0 mg/kg) or with its vehicle (0.9% NaCl solution plus Tween-80) from day 1 of pregnancy until delivery. Results show that prenatal aldrin administration was able to decrease the median effective time (TE50) for incisor teeth eruption and to increase the TE50 for testes descent; other parameters indicative of physical development were not modified. Aldrin and dieldrin were not found in plasma of the adult rats; no differences were observed between control and experimental rats in the cellular and structural organization of the cerebral cortex neurones. Prenatal aldrin administration produced no impairment of adult animal's behavior in an avoidance learning test; nevertheless, the locomotor frequency of the experimental rats was higher than that of controls at 21 and 90 days old. When adults, these experimental rats had their performance in a hole-board apparatus (total number and duration of head-dips) also higher than that of the control ones. It was concluded that prenatal aldrin exposure induced not only developmental changes in the rat pups but also persistent behavioral alterations in adulthood, when the pesticide was not present in these animals.

Aldrin↗