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The effect of lithium chloride on one-trial passive avoidance learning in rats.

1 Expression of a one-trial passive avoidance learning response in rats was examined following injections of lithium chloride or sodium chloride before and after initial training and before the first day of testing. Five tests were given at daily intervals, 24 h after training being the time of the first test. 2. Lithium given before the first day of testing impaired response expression on the first and all subsequent days of testing; the rate of extinction was unaffected. 3. Given both before and immediately after initial training, lithium impaired response expression on the first day of testing but slowed down the subsequent rate of extinction, leading eventually to improved performance on the fifth day, as compared with placebo-treated control subjects. 4. The results are interpreted in the light of the hypothesis that lithium impaired the central processing of sensory information.

Animals↗

Effects of nitric oxide on passive avoidance learning in rats.

To investigate the effects of nitric oxide (NO) on passive avoidance learning, L-NAME, D-NAME, and L-arginine were administered i.p. 30 min prior to learning trial; the effects of these substances were tested 24 h later using a passive avoidance apparatus in rats. To reveal the effect of NO on consolidation of acquired memory, L-NAME, D-NAME, and L-arginine were administered i.p. immediately after learning trials and animals were tested 24 h later. Effect of NO on retention was also investigated by injecting L-NAME, D-NAME, and L-arginine (same dosages) 30 min prior to 24 h testing (retrieval). L-NAME administered 30 min before and 24 h after learning trial significantly decreased the avoidance latency but there was no significant effect on consolidation. L-Arginine appeared to enhance the retention of acquired memory significantly, whereas D-NAME had no effect on any testing regime. The results suggest that NO may be involved in learning and retention of passive avoidance.

Animals↗

The inhibitory influence of an acquired escape strategy on subsequent avoidance learning in gerbils.

In gerbils an acquired non-avoidance strategy as pre-experience in a shuttle-box was studied in its influence on the learning of a standard avoidance paradigm. Thereby the same cue stimuli, frequency modulated tones (CS) and electric footshocks (US) were used in different behavioral paradigms. In the preexperience sessions the interstimulus interval between CS and US and on the other hand the escapability or inescapability of the US was varied. It was found that the experience with a relatively long interstimulus interval led to a prolonged maintenance of an acquired escape strategy during subsequent standard avoidance learning. This effect increased with the preexperience of an inescapable US. Additional insights into the temporal inhibition of avoidance learning by the pre-experience were provided by behavioral events like attention responses and orienting responses reflecting components of information processing.

Acoustic Stimulation↗

Mediation of passive avoidance learning by nicotinic hippocampo-entorhinal components in young rats.

Young rats, 11, 16, and 20 days of age, received bilateral injections of three antinicotinic agents into the posteroventral hippocampo-subiculo-entorhinal area, and were trained to learn a cool-draft-stimulus, passive-avoidance task shortly after (17 min). Gallamine triethiodide had no action at low doses and provoked convulsions at higher concentrations. Pempidine tartrate produced age- and dose-dependent impairments of the passive avoidance, and was much more effective in younger groups (11 and 16 days) than at 20 days. alpha-bungarotoxin also induced dose-dependent deficits. These results, together with the mecamylamine-induced deficits already reported, suggest that nicotinic cholinergic synapses located in the posteroventral part of the hippocampal complex play a role in passive-avoidance learning in the young rat as soon as this type of conditioning is possible, but become relatively less important at older ages, when muscarinic mechanisms also become involved.

Age Factors↗

Behavioral activity and active avoidance learning and retention in rats neonatally exposed to painful stimuli.

Twice daily for the first 15 days after birth, rats from the same litters were either placed for 5 sec on a hot plate (55 degrees C) (treated group), or on a plate maintained at body temperature (38 degrees C) (manipulated group). Controls were left undisturbed. When 90 days old, they were studied for pain threshold, open-field behavior, and two-way active avoidance learning and retention. Weight gain, pain threshold, open-field behavior, and active avoidance retention were not significantly different in the three groups. On the other hand, the rate of two-way active avoidance learning was significantly greater in treated rats. These results suggest that repeated neonatal exposure to painful stimuli, in rats raised under otherwise normal conditions, improves later active avoidance performance. The most likely mechanisms are discussed.

Acoustic Stimulation↗

2-Amino-4-phosphonobutyric acid selectively blocks two-way avoidance learning in the mouse.

There seems to be ample evidence supporting the view that glutamate plays a significant role in the mammalian brain as a neurotransmitter. It is considered to be a likely transmitter candidate in one or more hippocampal pathways. Recently it has been visualized in excitatory, possibly glutamatergic, neurons in the hippocampus. Glutamate has been proposed to mediate memory formation. We wanted to see if blocking glutamate action by a specific glutamate antagonist could result in reduction of learning ability. 2-Amino-4-phosphonobutyric acid (APB) is an analogue of glutamic acid and has been used as a glutamate antagonist in electrophysiological studies on invertebrate neuromuscular junction, retina and hippocampus. We tested the influence of APB on the acquisition of two way avoidance learning in the shuttle box and on learning in the water maze. Our results show that intraperitoneal injection of APB led to a reduction in avoidance learning, whereas learning in the water maze was unaffected.

Aminobutyrates↗

Leg position learning by an insect. I. A heat avoidance learning paradigm.

A new learning paradigm which employs a natural aversive stimulus, tightly constrains learned behavior and demonstrates learning in individual animals is described. Locusts were restrained so that only the femoro-tibial joint of a single metathoracic leg was free to move. Animals were required to maintain a particular range of femoro-tibial joint angle to avoid heating of the head. The position of the tibia was sampled by an on-line computer which set the limits of joint angle and controlled the aversive stimulus while storing data for further analysis. Control animals received patterns of aversive stimuli identical to those received by experimental animals but independent of their own joint position. Quantitative evaluation of the learned behavior of individual animals allowed the identification of three different behavioral strategies by which learning was achieved.

Animals↗

Blockade of bombesin-like peptide receptors impairs inhibitory avoidance learning in mice.

Several studies reported that peripheral administration of bombesin (BN) and gastrin-releasing peptide (GRP) improved some forms of memory performance. In the present study, we examined the role of endogenous BN-like peptide(s) for the acquisition of inhibitory avoidance learning in mice using BN-like peptide receptor antagonists. An administration of [Leu(13)-(psi-CH(2)NH)-Leu(14)]BN (antagonizes GRP-R>neuromedin B receptor (NMB-R)) impaired the performance of inhibitory avoidance learning in all doses (16, 32, 64 nmol/kg). While the effect was somewhat lesser than [Leu(13)-(psi-CH(2)NH)-Leu(14)]BN, BIM23127 (antagonizes NMB-R>GRP-R) also impaired performance in a moderate dose (32 nmol/kg). These results showed that endogenous BN-like peptides have some role(s) for the modulation of learning and memory, and suggest that NMB/NMB-R pathway may also be involved in the memory acquisition and modulation as well as GRP/GRP-R pathway.

Animals↗

Defensive copers show a deficit in passive avoidance learning on Newman's go/no-go task: implications for self-deception and socialization.

The present study investigated whether passive avoidance learning was retarded by defensive coping strategies designed to minimize exposure to negatively valenced stimuli. High-anxious individuals, low-anxious individuals, and defensive copers completed a computerized go/no-go task, in which they learned when to press or not to press a button, in response to contingent positive and negative feedback. The duration that feedback remained onscreen was self-regulated. Defensive copers showed preferential reflection away from negative feedback, committed more passive-avoidance errors, and were characterized by impaired learning, overall. Further, the ratio of reflection on negative feedback to reflection on positive feedback directly mediated both passive-avoidance errors and overall learning. Defensive coping strategies, therefore, appear to interfere with passive avoidance learning, thereby fostering perseverative, dysfunctional action patterns by reducing knowledge gained from previous mistakes. Implications for the learning of effective socialization strategies, and for psychopathy-which is commonly characterized by similar passive-avoidance deficits-are subsequently considered.

Adaptation, Psychological↗

Role of hippocampal NO in the acquisition and consolidation of inhibitory avoidance learning.

Nitric oxide (NO), an unconventional neurotransmitter in the brain, has been postulated as a retrograde intercellular messenger necessary for the induction, but not the maintenance phase, of activity-dependent forms of synaptic plasticity in the hippocampus. Here we report on the effects of an inhibitory avoidance learning task on hippocampal NO synthase (NOS) activity and on the effects of intrahippocampal infusion of a NOS inhibitor in the acquisition and consolidation of this task in rats. NOS activity increases by 45% in the hippocampus immediately after training (0 min) but not at 60 min after training. No changes were observed in cerebellar NOS activity. The bilateral intrahippocampal microinjection of nitro-arginine (NO-arg), an NOS inhibitor, provoked retrograde amnesia for the inhibitory avoidance when given 10 min before or immediately after training, but not 60 min after training. These results suggest that NO-regulated processes in the hippocampus play an important role at the time of training or very shortly thereafter of an inhibitory avoidance learning.

Animals↗

Intraperitoneal injection of 1-oleoyl-2-docosahexaenoyl phosphatidylcholine enhances discriminatory shock avoidance learning in rats.

Effects of injection of 1-oleoyl-2-docosahexaenoyl-sn-glycero-3-phosphorylcholine (ODHPC) on learning ability were investigated in rats using discriminatory shock avoidance learning task. When ODHPC (2 mumol) was intraperitonealy administered 5 min before the beginning of the first trial of learning task from the second to fifth sessions, avoiding rates of the ODHPC-injected group were significantly higher than those of the control group. However, any injection of ODHPC derivatives, such as 1-oleoyl-2-docosahexaenoyl-diacylglycerol, 1,2-dioleoyl-sn-glycero-3-phosphorylcholine, glycerophosphorylcholine, docosahexaenoate, oleate and choline chloride, did not affect learning. These results suggest that intraperitoneal ODHPC injection enhances learning ability by its specific conformation.

Animals↗

Passive-avoidance learning after medial septal lesions: effect of experience and the peripheral sympathetic nervous system.

Prior studies from our laboratory suggest that peripheral sympathetic ingrowth, which occurs in the hippocampus following medial septal lesions, is detrimental to the reaquisition of a spatial learning/memory task. To assess the generality of this finding we studied step-through passive-avoidance learning in animals with a medial septal lesion with or without superior cervical ganglionectomy under two experimental conditions. In the first condition, in which no prior experience with the task occurred, animals with a lesion demonstrated facilitation of learning. In the second condition, in which animals received pretraining with no shock prior to surgical manipulation, the behavior of animals with the lesion was similar to that of controls. No effect of ganglionectomy or initial sympathetic ingrowth was found in either condition. The results suggest that the effects of medial septal lesions on passive avoidance behavior are determined by the experimental condition and that early peripheral sympathetic ingrowth does not contribute either in a detrimental or beneficial fashion to passive avoidance learning.

Animals↗

The effects of estradiol on avoidance learning in ovariectomized adult rats.

The present study examined the effects of ovariectomy and subsequent estradiol replacement on learning in young adult rats using a set of instrumental avoidance paradigms differing in the nature and extent of prior experience in the learning context. Thus, one group of animals was placed directly into avoidance learning (AV). A second group was trained on an appetitive task first, and then transferred into the aversive context (AP-AV). The third group was exposed to the training context without any specific appetitive response requirement, and then required to learn an active avoidance response (Context-AV). We found that estradiol (OVX+E) impaired avoidance acquisition in all cases relative ovariectomized controls (OVX). In contrast, while avoidance learning is improved following appetitive training or context exposure in both OVX+E and OVX animals, the OVX+E animals profit to a greater extent from the appetitive or context experience than do the OVX controls. We suggest that this difference may be due to enhanced attentional processes or improved hippocampal processing of contextual factors. Thus, estradiol negatively influences simple associative avoidance learning in ovariectomized rats, but appears to promote positive transfer.

Animals↗

Hippocampal cGMP and cAMP are differentially involved in memory processing of inhibitory avoidance learning.

Cyclic GMP (cGMP) and cyclic AMP (cAMP) have been proposed to participate in the early and late stages of long-term potentiation (LTP), respectively. Here we report on the effect of post-training intrahippocampal infusion of membrane-permeable analogues of these cyclic nucleotides on the consolidation of inhibitory avoidance learning in rats and on the effect of this task on hippocampal cGMP and cAMP levels. Bilateral intrahippocampal microinjection of 8 Br-cGMP (1.25 micrograms per side) enhanced retention test performance when given immediately (0 min), but not when given 180 min, after training. In marked contrast, intrahippocampal infusion of the same dose of 8 Br-cAMP facilitated memory consolidation when given 180 min, but not 0 min, after training. Rats submitted to an inhibitory avoidance task showed a significant increase in the amount of cGMP in the hippocampus at 0 and 30 min after training, and in the amount of cAMP 30 and 180 min after training. Taken together, these results indicate that cGMP-regulated processes in the hippocampus play an important role in the early stages of memory consolidation and that cAMP signalling pathways are involved in the late post-training memory processing of inhibitory avoidance learning.

8-Bromo Cyclic Adenosine Monophosphate↗

The role of telencephalic NMDA receptors in avoidance learning in goldfish (Carassius auratus).

Studies with goldfish (Carassius auratus) have suggested that N-methyl-D-aspartate (NMDA) receptors are concentrated most densely in the telencephalon, a simple structure homologous to the limbic structure of higher vertebrates. The present study investigated the amnestic effects of microinjections of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) to the goldfish telencephalon on avoidance conditioning. Results showed that microinjections of D-AP5 before training impaired avoidance learning at doses that did not impair performance processes. High-performance liquid chromatography measurements showed that D-AP5 was detected only in the telencephalon following microinjections. Thus, D-AP5 impaired avoidance learning through its interaction with telencephalic NMDA receptors in goldfish. Furthermore, microinjections of D-AP5 to the goldfish telencephalon immediately following training did not impair memory consolidation of avoidance conditioning.

Animals↗

Enhanced passive avoidance learning and appetitive T-maze learning with post-trial rewarding hypothalamic stimulation.

Experiments were carried out to investigate the effects of post-trial reinforcing stimulation of the lateral hypothalamus on learning in rats. The reinforcing stimulation was always presented for a duration of 20--30 sec (0.2 sec on/0.8 sec off), and was administered either immediately, 30 sec delayed or 300 sec delayed after exposure to the learning situation. In experiment 1 post-trial stimulation led to improved passive avoidance learning of an alcove-avoidance task when presented 30 sec compared to immediately after the footshock. In Experiment 2 reversal learning of a one-way shuttle-box avoidance task was facilitated by 30 sec delayed, but not 300 sec delayed post-trial reinforcing stimulation. In Experiment 3 appetitive left-right discrimination was investigated using a T-maze task. Thirty sec delayed post-trial reinforcing stimulation presented contingent on errors facilitated learning of this task. Together, the 3 studies provide further support for the hypothesis that reinforcers directly influence labile memory processes (such as short-term memory) and thereby improve learning.

Animals↗

Effects of fetal and early postnatal thiamin deficiency on avoidance learning in rats.

Thiamin deficiency was induced in two groups of young rats during two stages of growth: deficiency 1, from 8 days prepartum to 10 days postpartum or deficiency 2, from 1 to 18 days postpartum. The deficiency was reversed by thiamin injections for 5 days and return to a normal diet following which animals were tested at 35 days of age. Body weights at 21 and 36 days of age were not significantly reduced by the deficiency nor was brain weight affected. Activity levels were not significantly reduced by deficiency 1 but were reduced in deficiency 2. Both active and passive avoidance learning were significantly impaired in both deficiency 1 and 2, a finding which could not be attributed to alterations in pain sensitivity, motor ability or reduced activity levels. The results indicate that the developing brain is vulnerable to reduced thiamin intake and that the period of vulnerability may be different for activity and avoidance learning.

Aging↗

Repeated toluene exposure and changes of response latency in shock avoidance learning.

Behavioral effects of repeated exposure to toluene were investigated. After 1, 3, and 6 weeks exposure to toluene at 1000 and 2000 ppm, all rats received shock avoidance training. Toluene-exposed rats could acquire shock avoidance learning and there was no significant difference between exposed rats and control rats. Analyzing response latencies (RLs) of avoidance responses, control rats shifted them to a longer RL and at last they learned to perform avoidance responses with specific RLs (3-4 sec). However, rats exposed to 1000 ppm toluene for 1 week and to 2000 ppm toluene for 1 week and 3 weeks, did not learn to respond with specific RLs. Rats exposed to 1000 ppm and 2000 ppm toluene for 6 weeks did not shift to longer RLs. It was suggested that repeated exposure to toluene vapor ranging up to 2000 ppm had no influence on the acquisition of shock avoidance learning, but caused some functional impairments of higher nervous functions.

Animals↗