Effects of kind of prior training and intersession interval upon subsequent avoidance learning.
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BACKGROUND: As the unitary theory of anesthesia gives way to the "multiple sites, multiple mechanisms" concept, the sites involved in mediating the components of anesthesia must be identified. In the current study, we test the hypothesis that the basolateral amygdala complex (BLAC) is a brain site involved with mediating propofol-induced amnesia. METHODS: Male Sprague-Dawley rats were divided into two groups, sham-operated control animals and rats given bilateral excitotoxic N-methyl-D-aspartate lesions of the BLAC. For each group, animals were given intraperitoneal saline or propofol (25 mg/kg) 5 min before inhibitory avoidance learning. Rats were given a foot shock (0.4 mA) upon entering the dark side of a two-sided apparatus. Rats could escape additional shock by returning to and staying in the light side. Training ended after shock avoidance for greater than 60 s. Memory was tested at 24 h. Longer latencies to enter the dark side 24 h after training imply better memory. RESULTS: Sham-saline-treated animals had a robust memory latency (median latency [interquartile range] = 300 [163-567] s). Sham-propofo-treated animals exhibited a significant anterograde amnesia (latency = 63 [14-111] s) (P < 0.05 vs. sham-saline-treated animal). Both the saline-injected and propofol-injected animals with BLAC lesions showed robust memory (latency = 300 [264-485] and 323 [143480] s, respectively). These latencies did not differ from performance in the sham-saline-treated group and were significantly higher than the latency of the sham-propofol-treated group (both P < 0.05). CONCLUSIONS: Discrete BLAC lesions blocked the amnestic effect of propofol. BLAC activity appears to be a requirement for propofol-induced amnesia. This finding suggests that the BLAC is a key brain site mediating anesthetic-induced amnesia.
The effects of d-amphetamine dosage (0, 1, 3, and 5 mg/kg) and shock intensity (0.2, 0.5, and 0.8 ma) on the learning of a passive avoidance response were assessed in rats. A curvilinear dose-response relationship was found at all shock levels, showing slower learning under moderate doses of d-amphetamine. The lowest shock level produced slower learning, especially in conjunction with the lowest dose of d-amphetamine. Results are discussed in terms of freezing behavior.
Tested alone, in CD-1 mice, the nootropic drug oxiracetam (50 mg/kg) improved learning in a multitrial active avoidance task (shuttle-box), but did not affect one-trial passive avoidance acquisition. Nicotine, which was ineffective at the dose of 0.25 mg/kg, improved both active and passive avoidance at the dose of 0.5 mg/kg; 1 mg/kg nicotine still exerted facilitating effects on passive avoidance, but slightly depressed shuttle-box performance. Combinations of oxiracetam and nicotine improved passive avoidance more than either drug given separately. In the active avoidance task, a combination of oxiracetam with the lower dose of nicotine exerted improving effects never observed with nicotine alone, even at higher doses. The nootropic drug also prevented the slight depressant action exerted by 1 mg/kg nicotine. Thus, contrary to what was previously supposed, at least in mice subjected to shuttle-box avoidance training, nicotinic activation does not appear as the main neurochemical mechanism involved in the action of oxiracetam. Perhaps, oxiracetam and nicotine activate different types of cholinergic mechanisms, but it cannot be excluded that other neurotransmitters, particularly catecholamines, may be involved in the avoidance facilitating effects produced by nicotine and by combinations of the two drugs.
Glucose and the acetylcholinesterase inhibitor tacrine were tested, alone and in combination, in mice of the CD-1 strain subjected to five daily shuttle-box training sessions. Pretraining intraperitoneal administration of glucose alone (50-400 mg/kg) had no significant effect, while tacrine alone (0.5-3 mg/kg) improved avoidance acquisition at the dose of 2 mg/kg only. Significant avoidance learning improvements were instead produced by 50 or 100 mg/kg glucose combined with 0.5 or 1 mg/kg tacrine. The effects on shuttle-box avoidance acquisition produced by glucose combined with a cholinomimetic agent support the hypothesis that cholinergic mechanisms may be involved in the action of glucose on learning and memory. However, the main finding of the present study is related to the enhancement by glucose of the learning improving action of a drug clinically used as cognitive enhancer.
Neuropeptide substance P (SP) has reinforcing and memory facilitating effects after its peripheral or central application. Rats self-inject SP into the ventromedial caudate-putamen and SP microinjections into the basal forebrain induce place preference with a simultaneous increase of dopamine level. In the amygdaloid body SP positive neurones and terminals have been identified. The aim of the present study was to examine the possible reinforcing effects of SP in the basolateral amygdala (ABL). CFY male rats were conditioned in two-compartment passive avoidance paradigm and place preference was examined in two-compartment-box and in circular open field. Animals were microinjected bilaterally with 10 ng SP, 100 ng SP or vehicle solution (0.4 microl/side) into the ABL. Results showed that post-shock infusion of 10 ng SP significantly enhanced passive avoidance learning while 100 ng SP was ineffective. In two-compartment-box and in circular open field place preference did not develop after SP treatments, however. Our data are the first to demonstrate that SP in the ABL is involved in learning and memory processes related to aversive situations. Results that SP microinjections were not followed by rewarding-reinforcing consequences in place preference paradigms indicate that the local SP network in the ABL is not involved in neuronal circuitry responsible for addictive behaviour.
Müllerian mimicry, where unpalatable prey share common warning patterns, has long fascinated evolutionary biologists. It is commonly assumed that Müllerian mimics benefit by sharing the costs of predator education, thus reducing per capita mortality, although there has been no direct test of this assumption. Here, we specifically measure the selection pressure exerted by avian predators on unpalatable prey with different degrees of visual similarity in their warning patterns. Using wild-caught birds foraging on novel patterned prey in the laboratory, we unexpectedly found that pattern similarity did not increase the speed of avoidance learning, and even dissimilar mimics shared the education of naive predators. This was a consistent finding across two different densities of unpalatable prey, although mortalities were lower at the higher density as expected. Interestingly, the mortalities of Müllerian mimics were affected by pattern similarity in the predicted way by the end of our experiment, although the result was not quite significant. This suggests that the benefits to Müllerian mimics may emerge only later in the learning process, and that predator experience of the patterns may affect the degree to which pattern similarity is important. This highlights the need to measure the behaviour of real predators if we are to understand fully the evolution of mimicry systems.
Portacaval-anastomized (PCA) rats were used to demonstrate the involvement of the serotonergic system in long-term memory formation. Significant increases in the concentration of 5-hydroxyindoleacetic acid, a metabolite of 5-hydroxytryptamine (5-HT), in all regions examined and the turnover rate of this indoleamine transmitter in the hippocampus, hypothalamus, midbrain and medulla oblongata were observed in PCA rats in comparison with sham-operated controls. Cyproheptadine, a 5-HT receptor blocking agent, impaired the retention of two-way avoidance learning reinforced by light stimuli when the drug was intraperitoneally injected immediately after the completion of training. PCA treatment attenuated the impairing effect of cyproheptadine. When cyproheptadine was injected 2 h after the completion of training, the correct response in the retention test period was not decreased. The present results suggest that memory formation is a time-requiring process and is mediated by the central serotonergic mechanism.
Substance P (SP) and an analogue (Lys-Phe-Ile-Gly-Leu-MetNH2 = EH) were tested in acute experiments on the blood pressure in the intact rat anaesthetized with urethane. A biphasic response, consisting of an initial depressor, followed by a pressor component, was seen. In low concentrations, SP decreases blood pressure, in medium concentrations SP produces a pronounced biphasic response, in high concentrations SP produces only hypertensive reactions. In chronic experiments, SP-peptides act also in different directions. After EH, disorders in avoidance learning were completely eliminated from 10 weeks old spontaneously hypertensive rats (SHR) or conditionally from SHR age 14 or 26 weeks. Elevated blood pressure in SHR aged 26 weeks was reduced by EH. Blood pressure in SHR aged 14 weeks was almost unaffected by EH and blood pressure went up in ten weeks old SHR. SP had a weaker action in comparison with EH. These results are in agreement with the hypothesis proposed by Oehme and co-workers [11-13] that SP can act as a regulatory peptide (="regulide").
Mice were trained to avoid footshock in a T-maze, with retention tested one week later. Adult male CD-1 mice made their first avoidance during acquisition after fewer trials than random cycling females and with less variability. Female mice in diestrus, when plasma levels of progesterone are low, learned to avoid footshock faster than females in estrus. Ovariectomized (OVX) mice learned in fewer trials than intact random cycling mice. Similar differences, though of a smaller magnitude, were found on the retention tests (i.e. males had better retention than females, mice in diestrus showed better retention 8 days later when in the same part of the estrous cycle than those in estrus, and OVX mice had better retention than cycling females). OVX mice with estrogen implants learned faster than those with progesterone implants or progesterone plus estrogen implants. Hormonal status did not affect sensitivity to acoustic or footshock stimuli as measured by a startle reflex, nor did it affect activity. Pretraining administration of amphetamine, picrotoxin and strychnine attenuated the impairing effect of progesterone on acquisition. The possibility that progesterone may impair learning and to some extent, retention by facilitating the GABAergic activity and thereby reducing arousal level is discussed.
The dams of each group of rats were given subcutaneous injections of diazepam (5 mg/kg), buspirone (10 mg/kg) or saline day 7 to 21 of their gestation periods. The intact group that received no injection was compared with the injection groups to evaluate the effects of stress caused by the subcutaneous injections. The brain concentrations of monoamines were investigated in 1-day-old female rats. Levels of tryptophan, 5-HT, 5-HIAA and 3-o-MDOPA decreased, but DOPAC increased in the saline group in comparison with the intact group. Tryptophan, 5-HT, 5-HIAA and 3-o-MDOPA increased in the diazepam group in comparison with the saline group. Tryptophan increased, and DOPAC, HVA and MHPG decreased in the buspirone group in comparison with the saline group. The avoidance learning test in a shuttle box was applied to 9-week-old offspring male rats. The saline group learning score had the poorest among the four groups. These results suggest that the prenatal stress of hypodermic injections may adversely affect the learning ability in the offspring. The two antianxiety drugs may overcome these adverse effects through reduction of prenatal stress.
Previous data indicate that learning of a conditioned visual avoidance task following simultaneous complete bilateral occipital ablations is affected by the age of the organism as well as the postoperative recovery period. The present study investigated the performance of the avoidance task, following complete occipital ablations, in young and older rats given two different recovery intervals. Young rats given 10 days to recover performed more poorly than the young control animals; given 20 days to recover, young rats performed comparable to controls. Older rats given 10 days to recover performed significantly better than the controls; given 20 days to recover, older rats did not show a decrease in performance. The present finding is consistent with previous data which show that the occipital cortex exerted an inhibitory effect on the learning ability of the avoidance task in older rats, which, upon removal, enhanced the performance of these rats on the task.
Behavioral animal paradigms and experimental neuroendocrinological and neurochemical studies have shown that early environmental manipulations have profound effects on the late response to stress. The aim of the present study was to investigate the interactive effects of environmental manipulation (early handling) and experimentally induced behavioral differences on the peripheral benzodiazepine receptor (PBR) system, which is known to be involved in the response to stressors. Adult early-handled (EH) and nonhandled (NH; control) Wistar rats were placed in a two-way active avoidance/latent inhibition (LI) paradigm, and PBR densities in the adrenal glands, kidneys, and gonads were assessed. In line with previous studies, overall avoidance learning improved in the EH group, and LI was disrupted in the NH group (primarily in males). PBR densities were up-regulated in EH subjects, and more so in females than males. However, PBR densities did not correlate with any of the behavioral measures. These findings strengthen the hypothesis that differences in PBR densities between EH and NH rats are a reflection of trait rather than state, and they suggest that the PBR system is characterized by a highly stressor-specific response.
1. The authors investigated whether learned helplessness was a possible explanation for the observed learning deficits demonstrated by autoimmune mice in shuttlebox avoidance. If mice were experiencing learned helplessness during the avoidance testing, one would expect this to transfer to other behavioral tests resulting in lower learning scores. 2. One group of BXSB mice was tested in avoidance first, a water version of the Lashley III maze second, and water escape last, while another group was given these tests in the reverse order. 3. Animals who were exposed to avoidance first did not demonstrate any learning deficits in subsequent tests, suggesting that there were no adverse effects of avoidance training on later water maze learning. 4. However, correlations between number of null responses during avoidance learning and two other measures suggest that the null response measure may be an index of a continuum of learned helplessness within the BXSB strain.
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The Roman high-avoidance (RHA) and low-avoidance (RLA) strains of rats were tested and compared with Maudsley reactive (MR) and non-reactive (MNR) strains to assess the relative contributions of emotionality and conditionability to differences between the two Roman strains. The RHA learned significantly faster in active avoidance, but slightly slower in passive avoidance, significantly faster in acquisition of an active approach task, but slighty slower in extinction of active approach tasks despite extensive adaptation and gentling. The RHA showed more 'rearing', more activity in the open field and more variety-seeking. Crossing with MNR showed the RHA less reactive in the open field. Results show RLA equivocal in conditionability, more emotional, and perhaps less active.
Long-Evans male rats were made hypothyroid from birth by the addition of 6-N-propylthiouracil (PTU) to their drinking water (0.1%). A group of animals was rehabilitated beginning at postnatal day 25 by withdrawal of the PTU from the drinking water. Subsequently, the rats were tested for a variety of behavioral tasks. Serum concentrations of thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) were determined by radioimmunoassay. At 50 days of age, PTU-treated rats had non-detectable levels of T4 but an eight-fold increase of TSH. In 50-day-old, neonatally hypothyroid but rehabilitated rats, serum TSH and T3 were normal, although T4 was still significantly lower. At 90 days of age, basal levels of TSH and thyroid hormones were normal in the rehabilitated rats, but thyroid hormone secretion in response to various types of neural stress was markedly altered. Comparison of passive avoidance learning revealed no significant alteration in the memory retention of either PTU-treated or rehabilitated animals. The 50-day-old, rehabilitated rats showed increased locomotor activity both in running-wheel and in hole-board tests; this hyperactivity, though markedly reduced, still persisted at day 90. In the early phase of rehabilitation (50 days of age), decreases in exploratory activity and lack of habituation occurred with the hole-board test; by the late phase of rehabilitation (90 days of age) these behavioral parameters had become normal. These results suggest generally longer periods of plasticity of the brain and better prospects for rehabilitation from neonatal cretinoid retardation than commonly believed. Specifically, the pituitary-thyroid system and neural mechanisms integrating adaptive behavior possess considerable capacity for spontaneous recovery from hypothyroidism; certain types of altered neuroendocrine and behavioral responses appear to be less amenable to rehabilitation or require longer periods for complete rehabilitation.
The relationship between the entorhinal cortex and learning behavior was examined. The initial stage of Alzheimer's disease has been shown to be characterized by neuropathological alteration in the entorhinal cortex, with the appearance of the greatest number of neuronal tangles and severe neuronal loss in comparison with other brain regions involved. This entorhinal cortex, because of its anatomical relationship to the hippocampus, may play a crucial role in memory formation. In this study, rats with bilateral ibotenic acid-induced lesions of the entorhinal cortices were tested for acquisition of passive and active avoidance learning tasks. These animals displayed no sensorimotor disturbances as shown by evaluation of locomotor activity and shock sensitivity. However, they did show impair acquisition of passive and active avoidance responses. On the other hand, when the lesions were induced after training, there was no extinction of the acquired passive and active avoidance responses. The results demonstrate the importance of the entorhinal cortex in learning acquisition and indicate that rats with partial neuronal loss in the entorhinal cortex may be a useful model for studying the memory disturbance of Alzheimer's disease.