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PubMed2002

Effect of ovariectomy and estrogen supplementation on brain acetylcholinesterase activity and passive-avoidance learning in rats.

The effect of ovariectomy and estrogen treatment on the brain acetylcholinesterase activity and cognition in rats was investigated in this study. Ovariectomized and nonovariectomized rats were treated subcutaneously with estradiol dipropionate for 8 d. In the single-trial, passive-avoidance test all the groups showed significant learning and retention of memory as evident by the increase in transfer latency time in trial 2 as compared with trial 1. No-transfer response was significantly increased in the estradiol-dipropionate-treated ovariectomized (80%) and nonovariectomized (60%) group as compared with the ovariectomized (30%) group. Specific activity of acetylcholinesterase was assayed spectrophotometrically in salt-soluble and detergent-soluble fractions of various brain areas: frontal cortex, cerebral cortex, striatum, hippocampus and hypothalamus, thalamus, pons, medulla, and cerebellum. The effect of ovariectomy and estradiol dipropionate was varied in both fractions of these brain areas. Estradiol dipropionate treatment could restore the acetylcholinesterase activity to the control level only in the detergent-soluble fraction of hypothalamus and salt-soluble fraction of hypothalamus, thalamus, and medulla in ovariectomized rats. The results indicate that ovariectomy alters acetylcholinesterase activity in the brain areas but not in a uniform manner and affects only qualitative aspects of cognitive function, which could be improved by estrogen supplementation.

Acetylcholinesterase↗

PubMed1976

[Effect of noncontingent electric shocks on subsequent avoidance learning in the rat, in a maze situation].

Rats were put in a Y maze and then pretreated with 0, 1, 3, or 10 noncontingent electric shocks. One day later, they were given an avoidance conditioning in the same apparatus. The 1-preshock group performed as well as the o-preshock group (control group). As compared to the control group, we found a facilitation of the avoidance response in the 3-preshock group and an impairment of the escape response in the 10-preshock groups. The impairment was still shown by the subjects when 3 weeks elapsed between the 10-preshock session and the learning session.

Animals↗

PubMed1998

The modulatory effects of high affinity GABA(B) receptor antagonists in an active avoidance learning paradigm in rats.

It has been reported that selective GABA(B) receptor antagonists can enhance cognitive performance in a variety of learning paradigms. This prompted us to examine the effects of some more potent and newly synthesised GABAB antagonists CGP 71982, CGP 62349 and CGP 55845A in an active avoidance test in rats. A two-way active avoidance test with negative reinforcement was performed for the first 5 of 12 days of antagonist administration. CGP 71982 and CGP 55845A at all doses applied (0.01-1.0 mg/kg) had an improving effect on learning, and memory retention on day 12; the rats made more avoidances in both sessions compared to controls. CGP 62349 was only active at the lowest dose tested (0.01 mg/kg). The present study confirms that GABA(B) receptor antagonists can enhance cognitive performance but provides no insight into the mechanism of action of these novel antagonists.

Animals↗

PubMed1994

Role of cholinergic neurotransmission in the amygdala on performances of passive avoidance learning in mice.

To clarify the role of cholinergic neurons in the amygdala on learning and memory, scopolamine was injected topically into the bilateral amygdala of mice, and the ability to perform two types of passive avoidance tasks (step-through and step-down) was investigated. On the first day mice performed the learning trial and on the second day their retention was tested. Scopolamine (0.5 or 1 microgram/site) was injected bilaterally into the amygdala 30 min before or immediately after the learning trial or 30 min before the testing trial. Scopolamine impaired the performance ability of the mice dose-dependently only when it was injected 30 min before the learning trial. The results coincided well with the effect of scopolamine injected intraperitoneally. Taken together, these results suggest that the site of action for scopolamine to cause anterograde amnesia is the amygdala, and that cholinergic neurons projecting to the amygdala play an important role in memory acquisition in the two passive avoidance tasks.

Amygdala↗

PubMed1985

Central serotonin neurones in avoidance learning: interactions with noradrenaline and dopamine neurones.

The effects of p-chloroamphetamine (PCA), a serotonin (5-HT) releaser, on acquisition and retention were examined in male Sprague-Dawley rats using a one-way active avoidance task. PCA was found to impair avoidance acquisition and retention in a time dependent fashion which followed closely the temporal effects of the drug on 5-HT release in the brain. Thus, the avoidance deficit is related to the rate of change and not to the steady-state levels of 5-HT. The 5-HT releasing effect was most pronounced in the forebrain with less effect in the spinal cord. PCA caused time dependent, regional variations in catecholamine content, which was not related to avoidance performance. The avoidance and retention impairment induced by PCA was blocked by the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) but not by depletion of catecholamines with alpha-methyl-p-tyrosine (H44/68) or by the noradrenergic-selective neurotoxin DSP4. Analysis of the time dependent effects of PCA on monoamine content in saline or PCPA-treated rats indicated that the temporal effects of PCA on avoidance performance is not due to a direct or indirect action on catecholamine neurones. The present experiments support the view that the ascending serotonergic pathways play a significant role in aversive learning in the rat.

Afferent Pathways↗

PubMed2001

Comparability of a single-trial passive avoidance learning task in the young chick across different laboratories.

The discrepant results noted by the La Trobe/Monash, Sussex, Open, and Berkeley University memory research groups employing the passive avoidance task (PAT) with the chick indicate that some of these differences may be due to differences in training procedures between the various groups. The procedures employed by each group were replicated as closely as possible and compared using the same strain of chick. Higher levels of pecking and lower training latencies were observed in the La Trobe/Monash chicks. Improved training latency was observed following a change in the day of experimentation with Sussex chicks, and in white light in Open chicks. A powerful reinforcing effect was observed when pretraining was conducted with a wet lure across multiple pretraining trials, indicating the importance of this difference between groups. The observed impact on chick performance of these variables indicates that differences between PAT procedures may have important interactive effects with aversive learning. The results of data gathered using different procedures may only be superficially comparable, and further investigation of the effects of these variables is indicated.

Age Factors↗

PubMed1978

Proactive and retroactive effects of hippocampal stimulation on active avoidance learning, hippocampal EEG and brain acetylcholinesterase activity in cats.

The subject of this investigation were the effects of electrical stimulation of the hippocampus on the acquisition of active avoidance response (AAR) in a shuttle-box. The stimulation (200 microamperes, 50/s, negative rectangular pulses of 1.0 ms duration) was applied once for 10 s before or after each training session. It was found that the application of hippocampal stimulation before each session facilitated the acquisition of AAR; discontinuation of the stimulation after training did not cause a decrease of AAR performance. Application of the stimulation after each session inhibited learning in four out of six cats. However, the level of AAR performance increased rapidly in these cats after inversion of the trials-stimulation sequence. It was also found that the intensity of the somatic and vegetative symptoms evoked by stimulation (stupor, salivation, twitching of facial muscles, pupil dilatation, crying) increased gradually in successive experimental sessions, suggesting the development of the 'kindling effect in cats stimulated before each session. In cats stimulated after each session the intensity of these symptoms was greatly diminished as compared to sessions where the stimulation was not preceded by the avoidance training, or they did appear at all. However, normal sensitivity to stimulation returned after several applications of hippocampal stimulation before each experimental session. Electroencephalographic studies showed that hippocampal stimulation with the use of the same parameters as those used during training evoked hippocampal afterdischarges lasting 5-60 s. No changes of aceltycholinesterase activity in different brain regions were found in consequence of such stimulation.

Acetylcholinesterase↗

PubMed2002

Effects of chronic acetyl-L-carnitine treatment on brain lipid hydroperoxide level and passive avoidance learning in senescence-accelerated mice.

In the present study, we examined the effects of acetyl-L-carnitine (ALC) on the brain lipid hydroperoxide level and on passive avoidance performance in senescence-acceleration-prone 8 mice (SAMP8). Mice were treated intraperitoneally with either saline or ALC (100 or 400 mg/kg) three times a week up to 4 months of age (starting at 3 weeks of age). In 4-month-old SAMP8, the deficit in learning and memory seen in saline-treated controls was significantly ameliorated in 400 mg/kg ALC-treated SAMP8, and the brain lipid hydroperoxide level was significantly lower in the 400 mg/kg ALC-treated group than in the saline-treated controls. Administration of 100 mg/kg ALC to SAMP8 did not have significant effect on learning and memory performance or on the brain lipid hydroperoxide level (by comparison with the saline-treated controls). These results suggest that ALC has antioxidant activity towards oxidative stress, and that the improvement in cognitive ability seen with ALC may occur through an amelioration of cellular dysfunction via an inhibition of the increase in lipid hydroperoxidation observed in the brain tissue of untreated SAMP8.

Acetylcarnitine↗

PubMed1986

Simultaneous approach and avoidance learning in the teleost marine fish Serranus scriba Cuv.

The ability of the fish to discriminate between constant light (the conditional stimulus of food) and flickering light (the conditional stimulus of a painful electric shock) administered in random order during the same experimental sessions was investigated. Approaching the light for food and avoiding the shock by moving away from the light could be tought simultaneously, approach learning being faster.

Animals↗

PubMed1986

[Influence of ACTH on Kamin effect in passive avoidance learning in rats].

The purpose of the present experiments was to compare the validity of the associative or "state dependent learning" hypothesis and the nonassociative ones, which had been proposed to explain the Kamin effect. In Experiment 1, rats were given one-trial passive avoidance trial with one of the three shock intensities (0.5-, 1.0- and 2.0-mA), and then the retention test was given after either one of the intervals of 0.05-, 2.5- and 24-hr. The clear Kamin effect (U-shaped retention function) was obtained for the animals treated with the 2.0-mA shock. In Experiment 2, the adrenocorticotropic hormone (ACTH) was injected two hours before the retention test to investigate the involvement of adreno-pituitary system in the retrieval of the memory. The retention performances at the intermediate (2.5-hr) interval were reinstated, whereas those at the 24-hr interval were impaired, as a function of dosage of ACTH. The results of these experiments favored the associative or state-dependent learning hypothesis on the Kamin effect.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Effects of post-trial reinforcing vs. subreinforcing stimulation of the substantia nigra on passive avoidance learning.

Experiments were designed to investigate the role of post-trial reinforcing and subreinforcing stimulation of the substantia nigra on memory processing. Thirty sec post-trial reinforcing stimulation (0.2 sec on/1.8 sec off) impaired learning of response suppression in a step-down task compared to control animals as well as to animals stimulated at subthreshold current level (i.e., at 25% of the current level shown to maintain optimal self-stimulation in previously performed self-stimulation sessions). In a second small-box passive avoidance experiment, i.e., the alcove-avoidance task, opposite results were attained: Subreinforcing stimulation attenuated learning whereas neither suprathreshold stimulated animals nor control animals showed impairment of learning. The conclusions drawn from these results are as follows: Post-trial stimulation of the substantia nigra interferes with memory processing. This attenuation of learning is obviously task-dependent and can additionally be influenced by the quality of the stimulation, i.e., whether it is reinforcing or not. Possible explanations to account for these task-dependent and quality of stimulation-dependent effects of post-trial substantia nigra stimulation are discussed.

Animals↗

PubMed1986

Mechanism for food avoidance learning in the central pattern generator of feeding behavior of Pleurobranchae californica.

Food-avoidance conditioning in the mollusk Pleurobranchaea results in suppression of the feeding response to food stimuli. In conditioned animals, identified interneurons of the central pattern generator (CPG) for feeding behavior, the Int-2s, respond to a food stimulus with greater and more long-lasting excitation than controls. Enhanced Int-2 responsiveness to food stimuli is associated with markedly heightened Int-2 excitability. Sustained activity in the Int-2s arrests motor output of the oscillatory CPG in the protraction/retraction movement cycle of feeding through tonic excitation of a population of retractor interneurons and inhibition of protractors. The CPG locus of the learning mechanism is permissive of sensory excitation of alternative behavior and leaves the possibility open for release of the suppressed behavior in a fully aroused state.

Journal Article↗

PubMed1982

Age-dependent improvement in passive avoidance learning of the young chick: cholinergic mediation?

Cholinergic mediation of the age-dependent improvement in response suppression of the young chick was studied by determining the performance of 4-day-old chicks, pretreated with scopolamine, during passive avoidance (PA) and extinction testing. In Experiment 1, chicks were trained briefly to key peck for heat reward (prepunishment training), and then tested for PA learning under immediate, 2-sec-delayed, or no shock condition. Half of the chicks in each wing-shock (5 mA, 5 sec) condition received saline injections before prepunishment training and .5 mg/kg scopolamine injections after prepunishment training. The rest of the chicks received .5 mg/kg scopolamine injections both before and after prepunishment training. For chicks in both scopolamine groups, delaying shock onset resulted in significantly less response suppression than immediate response-contingent shock. In Experiment 2, 4-day-old chicks injected with either saline or scopolamine were trained to key peck for heat reward and then tested for resistance to extinction under either response-contingent shock or nonshock conditions. Punishment decreased the number of extinction responses for both saline and scopolamine groups of chicks. Previous studies have shown that normal 1-day-old chicks do not show a significant delay of punishment effect during PA testing and that response-contingent punishment increases the number of their responses during extinction. Hence, the results of the present experiments indicate that the age-dependent improvement in response suppression of the young chick cannot be explained solely by a significant increase in central cholinergic functioning.

Aging↗

PubMed2001

Differential effects of lead and zinc on inhibitory avoidance learning in mice.

We studied the effects of chronic intoxication with the heavy metals lead (Pb2+) and zinc (Zn2+) on memory formation in mice. Animals were intoxicated through drinking water during the pre- and postnatal periods and then tested in the step-through inhibitory avoidance memory task. Chronic postnatal intoxication with Pb2+ did not change the step-through latency values recorded during the 4 weeks of the test (ANOVA, P>0.05). In contrast, mice intoxicated during the prenatal period showed significantly reduced latency values when compared to the control group (day 1: q = 4.62, P<0.05; day 7: q = 4.42, P<0.05; day 14: q = 5.65, P<0.05; day 21: q = 3.96, P<0.05, and day 28: q = 6.09, P<0.05). Although chronic postnatal intoxication with Zn2+ did not alter a memory retention test performed 24 h after training, we noticed a gradual decrease in latency at subsequent 4-week intervals (F = 3.07, P<0.05), an effect that was not observed in the control or in the Pb2+-treated groups. These results suggest an impairment of memory formation by Pb2+ when the animals are exposed during the critical period of neurogenesis, while Zn2+ appears to facilitate learning extinction.

Animals↗

PubMed1984

Time-dependent effects of hippocampo-entorhinal atropine on passive avoidance learning in the young rat.

Young rats 20 and 16 days of age received bilateral micro-injections of saline or atropine (115 micrograms/kg) into the posteroventral hippocampo-subiculo-entorhinal area, and were trained on a cool-draft-stimulus passive avoidance task thereafter. The delay between injection and training was variable: 17 min, 4 h and 6 h at 20 days; 17 min, 6 h and 12 h at 16 days. Atropine-induced learning deficits were observed after the short and intermediate intervals, but not after the longer ones, indicating that the action of atropine injected intracerebrally lasted for several hours (at least 4 h at 20 days, and 6 h at 16 days) and was over after 6 h and 12 h respectively.

Animals↗

PubMed2000

Post-trial sleep sequences including transition sleep are involved in avoidance learning of adult rats.

High resolution computerized EEG analyses, and behavioral observations were used to identify slow wave sleep (SS), paradoxical sleep (PS) and transition sleep (TS) in adult male Wistar rats exposed to a session of two-way active avoidance training. Of the four sleep sequences that could be identified, two included TS (SS-->TS-->W and SS-->TS-->PS), while the other two did not (SS-->W and SS-->PS). Comparison of post-trial sleep variables between fast learning rats (FL, reaching criterion in the training session), slow learning rats (SL, reaching criterion in the retention session the following day), and non learning rats (NL, failing to reach criterion) indicated that the total amounts of SS, TS and PS of the SS-->TS-->PS sequence was markedly higher in FL rats than in SL rats. In addition, in comparison with the corresponding baseline period, the average duration and total amount of SS and TS episodes of the SS-->TS-->PS sequence increased in FL rats, while the number of SS-->TS-->W sequences decreased. On the other hand, the average duration of SS episodes increased in the SS-->TS-->W and SS-->W sequences of SL rats, and in the SS-->W and SS-->TS-->PS sequences of NL rats. Correlative analyses between number of avoidances and post-trial sleep variables demonstrated that avoidances were directly correlated with the duration of SS episodes of the SS-->TS-->PS sequence and with the duration of TS episodes of the SS-->TS-->W sequence, but inversely correlated with the number and amount of SS episodes of the SS-->W sequence and with the duration and amount of SS episodes of the SS-->PS sequence. On the whole, the data supported the view that TS-containing sleep sequences are involved in long-term storage of novel adaptive behavior, while sleep sequences lacking TS are involved in the maintenance of innate behavioral responses.

Animals↗

PubMed1986

Food avoidance learning is accompanied by synaptic attenuation in identified interneurons controlling feeding behavior in Pleurobranchaea.

Identified paracerebral feeding command interneurons (PCNs) in the brain of the mollusc Pleurobranchaea excite other identified PCNs by means of a chemical polysynaptic pathway whose efficacy is reduced by food avoidance training (conditionally paired food and electric shock). The purpose of the present study was to identify the neurons comprising this pathway and to localize learning-induced changes to single identified neurons. We found that associative training strongly attenuates or abolishes a unitary excitatory postsynaptic potential (EPSP) at a single identified synapse in this polysynaptic pathway, but does not alter other synapses. The PCNs descend to the buccal ganglion, where they monosynaptically excite each member of a set of four identified neurons (two per hemiganglion) that belong to the corollary discharge population described previously. The strength of ascending and descending synapses involving identified PCNs is greatest ipsilaterally and is proportional to relative command efficacy established in previous studies. These findings suggest that command efficacy results directly from synaptic strength. The pair of corollary discharge neurons on each side of the buccal ganglion sends axons to the opposite side and thence up the contralateral cerebrobuccal connective to the brain. These neurons have therefore been termed the contralateral corollary discharge (CCD) neurons. Each CCD monosynaptically excites every PCN on both sides of the brain. Contralateral synaptic influences on identified PCNs are larger than ipsilateral ones. Each of the four identified CCD neurons is electrically coupled to all other members of the subset, including the contralateral homologue (based on simultaneous intracellular recording) and the ipsilateral partner (based on dye coupling). Hyperpolarizing a single CCD eliminates the polysynaptic response of PCNs to stimulation of other PCNs, whereas depolarizing a single CCD mimics the polysynaptic response. The CCD neurons are therefore necessary and sufficient to the polysynaptic response. Consistent with this role, the CCDs discharge in phase with the PCNs during the feeding motor program, and hyperpolarizing a CCD abolishes the cycle discharge of PCNs and weakens the feeding rhythm. Of the several reciprocal synapses identified between the PCNs and CCDs, only one was significantly altered by associative training in the food avoidance paradigm developed previously. This synapse, from the polysynaptic excitor (PSE) to the ipsilateral CCD, was also the strongest in this recurrent positive-feedback loop. In brains taken from conditioned specimens, the mean EPSP amplitude induced by a PSE action potential in ipsi

Action Potentials↗

PubMed2006

Space-time separation during obstacle-avoidance learning in monkeys.

Is the movement duration time known before we move? To answer this question, a new experimental paradigm is introduced that for the first time monitors the acquisition of a new motor skill in rhesus monkeys. Straight reaches were interleaved with reaches around physical obstacles that elicited a different path geometry. Curved and longer spatial paths were immediately resolved and consistent over months of training. A new temporal strategy separately evolved over repetitions from multiple to a single velocity peak. We propose that the obstacle-avoidance spatial paths were resolved before motion execution and used as reference in the computation of the new dynamics. Path conservation from the first trial occurred both at the hand and at the joint angle levels, whereas the speed profile dramatically changed over time. The spatial solution required no learning and was anticipated by the spontaneous repositioning of the initial arm posture. The learning was in the temporal domain, involving the adjustment of the speed during the motion's first impulse. Within the movement initiation, the partial distance traveled by the hand up to the first velocity peak was finely tuned under a constant time. For a given space location, the time of the first impulse remained robust to learning, but significantly shifted for different targets and obstacle configurations. Differences in the temporal-related parameters across time provided a clear distinction between learning and automatic behavior.

Algorithms↗