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PubMed1989

DPen2-[DPen5]enkephalin, a delta opioid receptor-selective analog of [Leu]enkephalin, impairs avoidance learning in an automated shelf-jump task in rats.

Both [Leu]enkephalin and DPen2-[DPen5]enkephalin, a delta opioid receptor selective analog of [Leu]enkephalin, impaired acquisition of an automated shelf-jump response in rats. A similar level of impairment was produced by equimolar doses of the two enkephalins. As is seen for [Leu]enkephalin when tested in a one-way active avoidance task, the dose-response function for the impairment produced by DPen2-[DPen5]enkephalin in the automated shelf-jump task is U-shaped. These results, together with our previous findings that DPen2-[DPen5]enkephalin and [Leu]enkephalin both impair acquisition of a one-way active avoidance response in mice, and that [Leu]enkephalin impairs acquisition of that same response in rats, support our suggestion that delta opioid receptors are implicated in the effects of [Leu]enkephalin on conditioning. In addition, these results indicate that the involvement of delta opioid receptors in acquisition impairment extends to two species of rodents and to two different avoidance conditioning tasks.

Animals↗

PubMedDate not supplied

EtOH self-administration on shuttle box avoidance learning and extinction in rats.

The effects of ethanol on the acquisition and extinction of the two-way active avoidance response were examined in adult, male Wistar rats from two treatment groups, oral self-administration of alcohol solution (10% v/v ethanol and 3% w/v glucose in distilled water) and oral self-administration of control solution (3% w/v glucose in distilled water). Alcohol or control solutions were available 1 h per day during 15 days simultaneously with food, with free water for the rest of the day. Blood was drawn in the last day of this phase to evaluate blood ethanol levels (BEL). After this period, rats were tested in a two-bottle paradigm for 1 h per day and placed in a shuttle box immediately afterwards. This phase went lasted for 10 days. Subjects were trained to avoid an electric foot shock in the first 5 days (15 trials per day). Following this, half of the subjects were tested in an "easy extinction with punishment" (EEP) and the other half in a "difficult extinction with punishment" (DEP) of the avoidance response for the last 5 days. Alcohol accelerates the avoidance responding acquisition, and no significant effects of alcohol were seen in the extinction phase. Data are discussed in terms of the specificity of the effects of alcohol on learning.

Animals↗

PubMed1987

Blockade of cholinergic receptors by an irreversible antagonist, propylbenzilylcholine mustard (PrBCM), in the rat cerebral cortex causes deficits in passive avoidance learning.

Studies were made on the effects of blockade of muscarinic acetylcholine (mACh) receptors in the rat cerebral cortex on learning and memory assessed by performance of a step-through passive avoidance task. Bilateral injection of propylbenzilylcholine mustard (PrBCM) into both the frontal and parietal cortex at doses of 2.25 X 4 to 22.5 X 4 micrograms decreased mACh receptors dose-dependently, as assessed by [3H]quinuclidinyl benzilate binding studies. When the training trial of a step-through passive avoidance task was performed 24 h after injection of 7.5 X 4 to 22.5 X 4 micrograms PrBCM into the frontal and parietal cortex, and then a retention test was made 24 h after the training trial, the treated rats showed shorter latencies than controls. In contrast, injection of PrBCM into the occipital cortex had no significant effect on performance in the test. These results confirm the notion that cholinergic neurotransmission in the cerebral cortex, especially the frontoparietal cortex, is important in learning and memory. The effects of injection of PrBCM (22.5 X 4 micrograms) into the frontoparietal cortex on 3 postulated phases of the learning and memory process (i.e. registration, retention and recall) were also examined. When PrBCM was injected 24 h before the training trial, no retention of the task was observed 14 days after the training trial. However, when PrBCM was injected 24 h after the training trial, retention of the task 14 days after the training trial was not affected. When PrBCM was injected 3-24 h after the initial training trial, the latencies in the retention test examined 24 h later were shorter than those of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Facilitatory effect of the dopamine D4 receptor agonist PD168,077 on memory consolidation of an inhibitory avoidance learned response in C57BL/6J mice.

The still unknown contribution of the D4 receptors to memory consolidation was studied examining the memory effects of the dopamine D4 agonist PD168,077, the putative dopamine D4 antagonist L745,870, their mutual combination, and the combination of the D4 agonist with representative compounds acting as agonist or antagonist on the D1, D2 and the D3 receptors. Memory consolidation was assessed in C57BL/6J mice using the one-trial step-through inhibitory avoidance task, the compounds being injected immediately after training (foot-shock) and performance measured 24h later. PD168,077 (0.5-10mg/kg) dose-dependently improved memory performance and L745,870 (0.05-5mg/kg) at doses lower than 1mg/kg increased and at doses higher than 1mg/kg impaired memory performance. PD168,077 did not affect the paradoxical promnesic effect of low doses (0.1-0.5mg/kg) of L745,870, but antagonised the memory-impairing effect induced by 5mg/kg L745,870. The D1 antagonist SCH23390 (0.025-0.05 mg/kg) and the D2 antagonist eticlopride (0.01-0.05 mg/kg) antagonised the promnesic effects of PD168,077, which attenuated the decreasing effect on memory consolidation of both D1 and D2 antagonists. Accordingly, the D1 agonist SKF38393 (5-20mg/kg) and the D2 agonist quinelorane (0.1-1 mg/kg) both synergistically magnified the memory-improving effects of the D4 agonist. The dopamine D3 antagonist U99194A (2.5-10mg/kg) did not affect the promnesic effects induced by the D4 agonist, which nevertheless abolished the U99194A-induced promnesic effects. Additionally, the amnesic effects produced by the D3 agonist 7-OH-DPAT (0.01-1 microg/kg) was attenuated by PD168,077. These results suggest a potential role of dopamine D4 receptors in memory consolidation, which would be similar to that of the D1 and D2 receptors and probably opposite to that of the D3 receptors.

Analysis of Variance↗

PubMed1999

Normal inhibitory avoidance learning and anxiety, but increased locomotor activity in mice devoid of PrP(C).

Prions are the causative agents of transmissible spongiform encephalopathies. The transmissible agent (PrP(Sc)) is an abnormal form of PrP(C), a normal neuronal protein. The physiological role of PrP(C) remains unclear. In the present report, we evaluated behavioral parameters in Prnp(0/0) mice devoid of PrP(C). Prnp(0/0) mice showed normal short- and long-term retention of a step-down inhibitory avoidance task and normal behavior in an elevated plus maze test of anxiety. During a 5-min exploration of an open field, Prnp(0/0) mice showed normal number of rearings, defecation, and latency to initiate locomotion, but a significant increase in the number of crossings. The results suggest that Prnp(0/0) mice show normal fear-motivated memory, anxiety and exploratory behavior, and a slight increase in locomotor activity during exploration of a novel environment.

Animals↗

PubMed1975

Conditioned drinking as avoidance learning.

Blocking the robust conditioned drinking response following conditioning eliminates the isotonic procaine conditioned response (CR) but not the hypertonic procaine CR. Rats allowed to drink in the box during conditioning form a larger CR than rats merely injected with hypertonic or isotonic procain who are prevented from drinking in the box: response blocking during extinction eliminated if no experience of drinking water in the box occurs either during baseline or during conditioning. Blocking the drinking response, like blocking shock avoidance, markedly reduces its high resistance to extinction. This suggests that rats overdrink to avoid anticipated illness, and fail to extinguish partially because they are never exposed to the fact that no illness will occur even if no drinking occurs.

Animals↗

PubMed1999

Effects of the novel acetylcholinesterase inhibitor N-octyl-1,2,3, 4-tetrahydro-9-aminoacridine on locomotor activity and avoidance learning in mice.

The acetylcholinesterase reversible inhibitor N-octyl-1,2,3, 4-tetrahydro-9-aminoacridine (THA-C8) is a new synthesized derivative of tacrine (THA) characterized by an alkyl chain in the molecular structure which ameliorates the penetrability of the compound into the central nervous system. THA-C8 (0.1-5 mg/kg) significantly reduced spontaneous locomotor activity in CD1 mice at a dose of 3 mg/kg. Moreover, THA-C8 (0.2-2 mg/kg) significantly improved shuttle-box avoidance acquisition at doses (0.25, 0.3, 1 mg/kg) not affecting locomotion and that are much lower than the doses reported to be effective for THA in animal models. From the data reported it seems that the new compound could be interesting for therapeutic purposes.

Alzheimer Disease↗

PubMed2000

Posttraining inactivation of excitatory afferent input to the locus coeruleus impairs retention in an inhibitory avoidance learning task.

These experiments examined whether the nucleus paragigantocellularis (PGi) contributes to memory storage processing via its ascending excitatory influence on locus coeruleus (LC) neuronal activity. Activation of the LC leads to memory enhancement and also results in a widespread release of norepinephrine in target structures, such as the amygdala and hippocampus. Infusion of norepinephrine into either structure also improves memory for several types of learned responses. Thus, the capacity for norepinephrine to modulate memory within limbic structures may be contingent upon the functional connections between PGi and the LC. To examine this hypothesis, male Sprague-Dawley rats were implanted with cannula aimed above PGi (Experiments 1 and 2) or 1.5 mm dorsal or medial to PGi (Experiment 3). Immediately following inhibitory avoidance training (0.45 mA, 0. 5 s), phosphate-buffered saline, lidocaine (Experiment 1), or 12.5 or 25 nmol/0.5 microl of the GABA agonist muscimol (Experiment 2) was infused into PGi. On a retention test given 48 h later, the latency to reenter the footshock compartment was significantly shorter for subjects given either lidocaine or 12.5 or 25.0 nmol of muscimol compared to controls. In Experiment 3, infusion of lidocaine or muscimol into areas 1.5 mm dorsal or medial to PGi did not significantly alter retention, indicating that the memory impairment observed in Experiments 1 and 2 was site specific and not due to the spread of drug to cell groups surrounding PGi. These findings suggest that PGi may serve a vital function in relaying biologically relevant information to forebrain structures involved in memory via its excitatory influence on the LC.

Anesthetics, Local↗

PubMed1983

Sex-linked differences in avoidance learning in the offspring of rats treated with nicotine during pregnancy.

The offspring of rats treated with nicotine (0.5 mg/kg/day SC) on days 1-20 of gestation, were trained for active avoidance conditioning when 60 days old. Although learning was similar in both control groups of males and females, nicotine exposure during fetal life improved learning in females but reduced it in males, the difference between these two groups being statistically significant from day 17 until the end of the training period (day 25).

Aging↗

PubMed1988

Ontogenetic development of avoidance learning in rats after eye opening.

Five male and one female group of 8 pups were selected from 8 liters on the second postnatal day and returned to 6 dams. The animals were investigated in two subsequent tests; first, in a peripheral field avoidance test using a 60 x 75 x 22 cm open field subdivided into 20 equal squares of 15 x 15 cm with separate floor grids for electrical punishment and, second, in a W-like maze with a start arm falling into a common alley from which left and right each two goal arms branched off. Four qualities were measured in the first test: finding out that only central fields remained unpunished; the stay duration in central fields indicating passive avoidance; the response to a conditioned stimulus, when they entered peripheral fields indicating active avoidance; the quality of extinction. The differences of these qualities changed significantly from week to week as the acquisition speed and the consolidation increased, the extinction was rapid in the third week, very slow in the fourth week and adult-like in the fifth week. The self-chosen strategy of pups showed dominance of escape with subsequent motor inhibition in the third week, dominance of trials and active avoidance in the fourth week, dominance of passive avoidance in the fifth week. We found no difference between males and females, or between blind and control rats. The W-maze test revealed additionally that reversal learning from left goal to right goal was still difficult in the fourth week and that brightness-cued alteration of goals in which wrong choices were punished when a time limit was overcome could not be learned before the sixth week and not consolidated before the end of the seventh week. The results suggest that various brain processes are involved in the development of avoidance and learning strategies which mature unevenly and reach their peaks at different ages.

Aging↗

PubMed1976

Activity, avoidance learning and regional 5-hydroxytryptamine following intra-brain stem 5,7-dihydroxytryptamine and electrolytic midbrain raphe lesions in the rat.

Rats underwent one of the following treatments: (1) electrocoagulation of both the dorsal and median midbrain raphe nuclei; (2) 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) injection (10 mug, as the salt, in 5 mul vehicle) into the vicinity of each midbrain raphe nucleus; (3) intra-brain stem vehicle (5 mul of 0.2% ascorbic acid in isotonic saline) injections; or, (4) a control operation. Open field activity and one-way avoidance conditioning were examined on postoperative days 16-23. Regional central 5-hydroxytryptamine (5-HT) and catecholamine (CA) concentrations were determined 25-27 days postoperatively. Regional 5-HT levels were greatly reduced following 5,7-DHT administration and electrolytic raphe lesions. The 5,7-DHT rats also showed a reduction in spinal 5-HT content. Central CA concentrations were not affected. Variation in the pattern of regional 5-HT changes after 5,7-DHT treatment was observed but appeared to be related to the adequacy of the dorsal raphe (B7) injection. Only the electrolytic raphe lesion animals, however, showed increased locomotor activity and retarded acquisition and forced-extinction of the one-way avoidance response. In contrast, no significant differences were observed in the open field and avoidance behavior of the 5,7-DHT, vehicle, and control groups. The hyperactivity and impaired one-way avoidance performance observed after electrolytic midbrain raphe lesions are not related simply to reductions in regional forebrain 5-HT and may well be due to damage of non-serotonergic neural systems. Clearly, the behavioral effects of central 5-HT depletion depend on the method employed. The role of 5-HT in regulating activity level and mediating avoidance behavior, furthermore, remains to be determined.

Animals↗

PubMed2005

Inhibition of endogenous carbon monoxide production induces transient retention losses in the day-old chick when trained using a single trial passive avoidance learning task.

Carbon monoxide (CO) is most often thought of as an exogenous toxin rather than as a possible endogenous nootrope. However, a limited number of studies have suggested that CO is necessary in memory processing for at least some tasks. While nitric oxide (NO) and CO are known activators of guanylyl cyclase (GC), only the effect of NO on GC has been extensively investigated as a mechanism underlying memory processing. The aim of the present study was to determine if inhibition of CO production would have an effect on memory processing. Using chicks trained on a single trial passive avoidance task, inhibition of CO production using zinc (II) deuteroporphyrin IX 2,4-bis ethylene glycol (ZnBG; 5 microM) resulted in two transient retention losses occurring at around 40 and 130 min post-training. The timing of these transient retention losses was similar to those observed following inhibition of GC, using the same species and task in a previous study. This supports the notion that CO is necessary in memory processing for this task and may act through a GC-dependent mechanism. As ZnBG also directly inhibits GC or nitric oxide synthase (NOS) at high concentrations, a second experiment was carried-out to confirm the specificity of ZnBG for heme oxygenase (HO) at the concentration used. The action of ZnBG was challenged with the HO agonist hemin (100 microM) and the transient deficits were abolished. This confirmed that the action of ZnBG on memory was through a CO-related mechanism rather than directly on GC or NOS. In this way the specificity of ZnBG (5 microM) for HO could be confirmed. The results support a role for endogenous CO in memory processing, possibly through activation of GC. In addition, the transient retention losses observed following administration of ZnBG suggest that CO may be necessary for memory retrieval and not formation as previously thought.

Animals↗

PubMed2003

Distinct roles of the different ionotropic glutamate receptors within the nucleus accumbens in passive-avoidance learning and memory in mice.

Research on the role of the nucleus accumbens in behaviour has been largely focused on the functions of this structure in conditioning to appetitive stimuli. It has been suggested that a network comprising the nucleus accumbens and its convergent inputs might mediate dissociable functions in the acquisition, the consolidation and the retrieval of information. However, findings related to a role of this structure in aversive conditioning are somewhat contradictory, and its involvement in this form of learning is still under debate. Moreover, very little evidence is available on the step of information processing mediated by the accumbens. Thus the purpose of this study was to investigate the effects of the blockade of the AMPA and NMDA glutamate receptors, which have been suggested to mediate the transmission of information from the limbic system to this structure, on a classical aversive conditioning task - the one-trial step through inhibitory avoidance paradigm (24 h interval between training and testing). Intra-accumbens focal injections of AP-5 and DNQX (NMDA and AMPA antagonists, respectively) were performed immediately after training, before training and before testing in mice. The NMDA antagonist (37.5, 75 and 150 ng per side) impaired animal performance only if administered immediately after but not before training or before testing. Conversely, DNQX (0.5, 1.0 and 5.0 ng per side) reduced the step through latencies when administered before training and before testing. These findings suggest that NMDA receptor activation within the accumbens is necessary in formation but not expression of memory for inhibitory avoidance. AMPA receptors, instead, are necessary for the acquisition and the expression but not consolidation of inhibitory avoidance memory.

Analysis of Variance↗

PubMed1999

Long-term voluntary ethanol consumption affects neither spatial nor passive avoidance learning, nor hippocampal acetylcholine release in alcohol-preferring rats.

Long-term ethanol consumption in humans and laboratory animals is associated with morphological and functional alterations of brain structures involved in cognitive processes. In the present experiments, we assessed whether voluntary long-term consumption of ethanol by alcohol-preferring (sP) rats under free choice condition with water (also) caused alterations in memory performance and hippocampal acetylcholine (ACh) release in vivo. A group of sP rats were offered a 10% v/v ethanol solution in a free choice with water for 36 weeks; controls had only tap water available. After withdrawal of ethanol, rats were tested in one trial passive avoidance test and thereafter were trained in a food-reinforced radial arm maze task for 12 days. One day after the last session in the radial-arm maze, rats were implanted with a microdialysis probe in the dorsal hippocampus and dialysate concentrations of ACh were measured. No significant differences were observed between sP drinking and control rats in retention latencies in the passive avoidance test, in radial arm-maze performance or in basal levels of hippocampal ACh release. These results show that long-term ethanol consumption by sP rats is not associated with cognitive impairments or with alterations in the hippocampal cholinergic function. To the extent that chronic ethanol intoxication can be considered a causal factor in the development of memory and neurochemical alterations, these results suggest that sP rats self-regulate ethanol consumption so as to avoid intoxication. These findings may challenge the notion that sP rat lines can be considered a valid model of human alcoholism.

Acetylcholine↗

PubMed1998

A characterization of approach and avoidance learning in alcohol-preferring and alcohol-nonpreferring rats.

Although numerous biochemical and physiological differences have been shown to be correlated with alcohol preference, less is known about behavioral factors that may correlate with alcohol preference. Using a signaled barpressing task, alcohol-preferring (P; n = 18) and alcohol-nonpreferring (NP; n = 19) rats were compared for their ability to learn an appetitive and an aversive task. Results showed that P rats had difficulty learning the tasks in comparison with NP and nonselected, control rats when appetitive training was given first. However, if aversive training came first, the NP rats performed poorly in comparison with the P and nonselected rats. These results suggest that these lines of rats may differ in behavioral inhibition and sensitivity to conditioned fear. Furthermore, these behavioral differences may offer a richer analysis of the traits that were co-selected with the alcohol-seeking and alcohol-avoiding phenotypes.

Alcohol Drinking↗

PubMed2003

Enhanced inhibitory avoidance learning prevents the memory-impairing effects of post-training hippocampal inactivation.

Rats were trained on an inhibitory avoidance task to study the effects of post-training administration of tetrodotoxin (TTX, which temporarily inactivates neural activity) on memory consolidation. During training, independent groups of rats received either a mild foot shock (0.8 mA) or a stronger (1.0 mA) foot shock. TTX was administered bilaterally into the dorsal hippocampus immediately after training, and memory of the task was measured 48 h later. We corroborated the typical amnesic effect of intrahippocampal infusions of TTX in those rats trained with the mild-intensity foot shock. More importantly, with the stronger foot shock, the same treatment was ineffective in producing amnesia. These results suggest that, after an enhanced learning experience, other brain regions are also activated, which may compensate for the amnesic effect of TTX infusions into the hippocampus.

Animals↗

PubMed1996

Changes in rat brain muscarinic receptors after inhibitory avoidance learning.

It is widely accepted that cerebral acetylcholine is necessary for learning and memory, but little is known about the type of muscarinic receptors involved in these functions. To investigate this problem, [3H]-N-methyl-scopolamine which binds to different types of muscarinic receptors, [3H]-Pirenzepine an M1 receptor antagonist, and [3H]-Oxotremorine-M which binds mainly to M2 receptors, were used as ligands to look for possible changes in muscarinic receptor density in neostriatum (NEO), hippocampus (HIP), amygdala (AMY), and temporo-parietal neocortex (CTX), after testing for retention of inhibitory avoidance, trained with high or low footshock intensities. After low reinforcement there was an M1 postsynaptic receptor up-regulation in NEO, HIP, and CTX, and an M2 presynaptic receptor down-regulation in HIP, which suggests a concerted pre- and postsynaptic cholinergic activation in this area. An up-regulation of both M1 and M2 receptors was detected in CTX of low and high footshocked animals, which indicates the presence of a cortical postsynaptic M2 receptor.

Amygdala↗

PubMed1979

Impairment of shuttlebox avoidance learning following repeated alcohol withdrawal episodes in rats.

Rats were reduced to 70% of their free-feeding body-weights and then randomly assigned to one of three groups. An Alcohol Withdrawal group was placed on a liquid diet consisting of alcohol plus Austagen for four 5-day periods interspersed with three 2-day periods of a liquid diet containing sucrose plus Sustagen. A Continuous Alcohol group received the alcohol diet for 20 days, followed by six days on the sucrose diet. A Sucrose Control group received diet only and was pair-fed the amounts consumed by the Alcohol Withdrawal group. Thirty days after the diets were discontinued the rats were given 60 trials on a shuttlebox avoidance task. The results showed that the Alcohol Withdrawal group was impaired in shuttlebox avoidance when compared to the Continuous Alcohol group and Sucrose Control group.

Animals↗