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Neonatal exposure to triethyltin disrupts olfactory discrimination learning in preweanling rats.

Triethyltin is an organotin compound that is known to produce neurotoxicity in both adult and developing organisms. Although this neurotoxicity has been documented with a variety of behavioral and biological measures, the effects of this compound on learning during early development have been less extensively studied. The present study reports four experiments that examined this question with an odor aversion learning paradigm in which pups received presentations of one odor paired with footshock and an alternate odor without shock. In Experiment 1, Long-Evans rat pups were injected IP on postnatal day 5 (PND 5) with either 0, 3 or 5 mg/kg TET and then tested for olfactory discrimination learning on PND 18. Only the 5-mg/kg dose impaired discrimination learning. In Experiment 2, PND 5 exposure to TET (5 mg/kg) disrupted olfactory learning on PND 18 but not on PND 12, whereas exposure on PND 10 disrupted learning at both ages of testing. In Experiment 3, PND 16 exposure to TET (5 mg/kg) also disrupted acquisition of olfactory learning on PND 18 but had no effect on retention of an olfactory discrimination that was acquired prior to TET exposure (i.e., on PND 14 and PND 15). Unconditioned responses to footshock were also unaffected by TET (Experiment 4). These findings indicate that neonatal exposure to TET impairs associative learning in developing rats and are discussed in relation to other studies of the developmental neurotoxicity of this compound.

Aging

Nalorphine as a stimulus in drug discrimination learning: assessment of the role of mu- and kappa-receptor subtypes.

Using the conditioned taste aversion baseline of drug discrimination learning, animals were trained to discriminate nalorphine from distilled water. In subsequent generalization tests, the mu-opiate agonist morphine substituted for the nalorphine stimulus in a dose-dependent manner, while the kappa-opiate agonist U50,488H and the mu-opiate antagonists naloxone and naltrexone failed to do so. That the mu-agonist morphine substituted for the nalorphine stimulus while a kappa-agonist and mu-antagonists failed to substitute indicate that the discriminative control that was established with nalorphine in the present study was mu-agonist receptor-mediated. The basis for this selective control by the mu-receptor subtype may be related to the relative salience of receptor activity in opiate-naive animals. The present results suggest that discriminative control by compounds with activity at multiple receptor sites is not uniformly mediated by specific activity at all of those sites. The specific site mediating discriminative control appears to be a function of the specific training drug.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Effects of discrimination learning on the rat amygdala dopamine release: a microdialysis study.

Extracellular levels of dopamine (DA) and its metabolites were monitored with the in vivo microdialysis method in the amygdala of rats while and after they performed a discrimination learning task or a non-discrimination task. A group of rats was trained to discriminate between lamp-on and lamp-off states under an operant-type learning procedure. After a stable discriminative behavior was established, a dialysis probe was inserted into the basolateral amygdaloid nucleus of each rat. The concentrations of DA and its metabolite 3,4-dihydroxyphenylacetic acid significantly increased during the learning sessions as compared to their basal levels. In contrast, another group of rats trained on a similar, but non-discriminative task showed no such increases. These results suggest that the dopaminergic neural systems in the basolateral amygdaloid nucleus are activated during ongoing behavior maintained under the discrimination learning situation.

Amygdala

Neonatal glutamate can destroy the hippocampal CA1 structure and impair discrimination learning in rats.

Neonatal Wistar rats were subcutaneously injected with 0.1, 1, or 2 mg/g b.wt. of monosodium glutamate (MSG) at 1, 3, 5, 7, and 9 days after birth. The animals were observed for degeneration of pyramidal cells in the hippocampus. The histological change disappeared when the animals were concurrently injected with glutamate diethyl ester (GDEE), an antagonist of the glutamate receptor. When light-dark discrimination learning was carried out at 10 weeks old, the correct response in the acquisition period was impaired in the animals given 1 and 2 mg/g of neonatal MSG. Their retention scores were also impaired in comparison with the control animal. The behavioral impairment recovered with pre-treatment with GDEE. No significant changes were observed in the concentrations of transmitter substances, including amino acids and monoamines. These results suggest that neonatal MSG destroys the hippocampus and impairs acquisition and retention of discrimination learning through the mechanism of glutamate receptors.

Animals

Buprenorphine as a stimulus in drug discrimination learning: an assessment of mu and kappa receptor activity.

Using the conditioned taste aversion baseline of drug discrimination learning, different groups of animals were trained to discriminate either buprenorphine or morphine from distilled water. Specifically, animals were injected with buprenorphine or morphine prior to a saccharin-LiCl pairing and the drug vehicle prior to saccharin alone. By the fifth conditioning trial, animals differentially consumed saccharin on the basis of administration of the drug or its vehicle. In subsequent generalization tests, buprenorphine stimulus control generalized completely to the mu agonist morphine in four of the five subjects tested, while morphine stimulus control completely generalized to buprenorphine in two of five subjects and partially generalized in the remaining three. Buprenorphine failed to generalize to the relatively selective kappa antagonist MR2266 and the broad-based antagonist diprenorphine. Morphine also failed to generalize to MR2266, but did generalize to diprenorphine. That morphine and buprenorphine displayed some degree of cross-generalization suggests that these compounds share some stimulus property, presumably their agonist activity at the mu receptor, and that the mu activity of these compounds was used in the establishment of the discrimination, a conclusion supported by the fact that compounds with mu antagonist activity (e.g., naloxone, MR2266) blocked both buprenorphine and morphine stimulus control. That buprenorphine failed to generalize to compounds with kappa antagonist activity suggests that animals trained to discriminate buprenorphine from its vehicle do not use the kappa antagonist activity of the drug in the establishment of the discrimination. The basis for the differential ability of various receptor subtypes to mediate the discriminative properties of compounds with mixed receptor activity was discussed.

Animals

Effects of dihydroergotoxine on central cholinergic neuronal systems and discrimination learning test in aged rats.

We evaluated changes in the cholinergic neuronal system and learning ability with aging. Choline acetyltransferase (ChAT) activity, a presynaptic index of the cholinergic system, was decreased in the cerebral cortex, hippocampus, striatum, and hypothalamus in the brain of aged rats compared with young adults. Muscarinic cholinergic binding sites (receptors, MCR), a postsynaptic index of the cholinergic system, were markedly decreased in all areas of the brain. However, intraperitoneal injection of 1 mg/kg of dihydroergotoxine (DHET) for 14 days normalized both ChAT and MCR in the cerebral cortex and hippocampus. In the striatum, ChAT was normalized, but MCR did not recover. Aged rats showed marked learning impairment in a 30-day operant type brightness discrimination learning test. Daily DHET administration restored the discrimination ability in the aged rats to nearly the young adult level. DHET had no effects on central cholinergic indices or learning test results in young adult rats. These findings suggest that learning is impaired in aged rats due to impairment in the central cholinergic neuronal system, and that DHET normalizes the decreased function in this system, restoring the learning ability.

Aging

Effect of piracetam, a nootropic agent, on discrimination learning deficits induced by parental undernutrition and environmental impoverishment in young rats.

The study was conducted on 64 Charles Foster albino rats which were equally distributed into 8 even-matched groups, following a 2 x 2 x 2 factorial design by varying three independent factors at two levels: nutrition--normal and undernutrition, environmental--enrichment and impoverishment, and drug treatment--vehicle and piracetam (100 mg/kg, ip). Prenatal nutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/drug treatments were given during the postweaning period of the rat pups. The animals were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. The results indicate that undernutrition and environmental impoverishment significantly attenuated the original discrimination as well as the reversal discrimination learning. Piracetam treatment improved the learning performance of normally reared rats and also attenuated the original and reversal learning deficits induced by prenatal undernutrition and postnatal impoverishment. The results indicate that piracetam may be useful in memory deficits induced by malnutrition.

Analysis of Variance

Genetic differences in avoidance learning by Rattus norvegicus: escape/avoidance responding, sensitivity to electric shock, discrimination learning, and open-field behavior.

The behaviors of rats selectively bred for either good or poor shuttle box avoidance learning were studied. The results of Experiment 1 indicated that the phenotypic difference in avoidance learning is not associated with differences in speed of escape or avoidance responding. Differences between the lines in frequency of intertrial responses (ITRs), which appear during training but not during pretest, suggest that ITRs in animals of the low-avoidance (SLA) line are more suppressed by electric shock than in animals of the high-avoidance (SHA) line. This result suggests that SLA animals may be more emotionally responsive than SHA animals. Experiment 2 demonstrated that the animals of the two lines do not differ in absolute sensitivity to electric shock, and Experiment 3 showed that the poor performance of the SLA line is not due to an inability to learn. Experiment 3 also provided evidence which suggests that the poor avoidance learning by SLA animals is due to their emotional reactivity. Observations of open-field behavior in Experiment 4 are consistent with this hypothesis. The major consistent correlate of the phenotypic difference in avoidance learning is greater emotionality or emotional reactivity in SLA than in SHA animals.

Animals

Delta-9-tetrahydrocannabinol impairs visual recognition memory but not discrimination learning in rhesus monkeys.

The effects of orally administered delta-9-tetrahydrocannabinol (THC) were evaluated on two different learning abilities in monkeys. Visual recognition memory, known to depend on limbic system integrity, was tested by means of delayed nonmatching-to-sample and found to be significantly impaired by acute administration of 2 and 4 mg/kg THC given 1 or 2 h prior to testing. Performance was significantly impaired throughout a 21-day period of repeated administration of 4 mg/kg THC and also during a 3-5 day period that began 7-10 days after the last dose of THC. By contrast, 24-h concurrent discrimination learning, a task that monkeys with limbic lesions can perform normally, was not impaired by THC, even following doses as high as 16 mg/kg. These results suggest that THC interferes with recognition memory more than discrimination learning, possibly reflecting a selective action of THC on limbic mechanisms.

Administration, Oral

Hippocampus and the blood supply to TE: parahippocampal pial section impairs visual discrimination learning in monkeys.

In the base of each temporal lobe in 4 monkeys (Macaca fascicularis) we sectioned the pia mater in an antero-posterior line along the most medial part of the inferior temporal visual association cortex (area TE), lateral to the parahippocampal cortex. This pial section interrupts the blood flow in branches of the posterior cerebral artery which cross the parahippocampal gyrus en route to area TE. Histologically, the brains of 2 of these animals did not show any abnormalities in cresyl violet stained material, apart from the small cortical damage along the line of the pial section itself. Of the remaining two animals, one had a small unilateral infarct in TE and one had bilateral infarcts in TE. All of these animals were impaired in visual discrimination learning, and the severity of impairment was correlated only imperfectly with the severity of infarction. These results show that pial section along the medial boundary of area TE can affect visual discrimination learning without producing large infarcts. Further, since aspiration lesions of the hippocampal formation require the pia mater to be sectioned in a similar way to that reported here, the effects of such aspiration lesions on visual learning and memory may be mediated in part by effects on TE.

Animals

Control of children's observing responses by information feedback during visual discrimination learning.

Four experiments examined the control of observing responses by information feedback during visual discrimination learning. Second-grade children participated in Experiment 1; kindergarten, second-, and fifth-grade children were subjects in Experiments 2 and 3, and grade 5 and adult subjects were tested in Experiment 4. In order to view the stimuli, subjects in Experiments 1, 2, and 3 activated lights in viewing boxes; in Experiment 4, stimulus fixations were measured using a corneal reflection technique. Fifth graders and adults observed the discriminative stimuli for longer times on trials following negative feedback than on trials following positive feedback; in contrast, kindergartener's observing was not affected by type of feedback. Second graders showed smaller and less reliable reactions to type of feedback than did older subjects. These results support the view that visual observing is controlled by cognitive processes associated with hypothesis testing.

Child

Operant conditioning after temporal lobe lesions in man: conditional and simple discrimination learning.

Temporal lobe lesions have been found to impair the acquisition of classical conditional discrimination learning in an eyelid conditioning paradigm, with sparing of simple eyelid conditioning. In the present study, subjects with left or right temporal resections were compared with normal controls on two operant conditioning tasks using a conditional and a simple discrimination paradigm analogous to the previously reported classical conditioning tasks. Subjects with right temporal lesions, and to a lesser extent those with left temporal lesions, were impaired relative to frontal lobe and control subjects in the acquisition of a conditional discrimination within an operant conditioning setting. A subsequent experiment showed that both left and right temporal lobe subjects were unimpaired on a simple operant discrimination task. These findings are compatible with theory relating hippocampal function to the learning of if-then rules.

Adult

Luck and learning: feedback contingencies and initial success in verbal discrimination learning.

Ninety undergraduate volunteers learned a 12-pair, low frequency, verbal discrimination list. The independent variables were feedback (positive only, negative only, or both) and initial success (17%, 50%, or 83% correct on trial one). With the total errors on nine trials as the dependent variable, the main effect of feedback was found to be not significant. The main effect of initial success was significant. Subjects who started at 50% correct had the most difficulty learning the list and subjects in the 83% correct condition learned quickest. The predicted interaction between feedback and initial success was not significant, even though the means for the three types of feedback at the 17% correct starting level reflect the expected differences. The results are interpreted as supporting the rule-use component of frequency theory. The relationship between initial success and subsequent performance appears to be curvilinear, rather than linear, as many theorists have assumed.

Discrimination Learning

[Investigation of cortical slow potentials during the delayed discrimination learning in monkeys].

Averaged slow potentials (SPs) were recorded at different training stages of delayed discrimination learning in two monkeys. The details of the task sequence was described in our previous work. It was found that at the early stages of the training the amplitude of SPs was very small, and it increased gradually with the increase of percentage of correct responses. The SPs recorded from the prefrontal cortex had the largest amplitude and there was no SPs recorded from the rear portion of the cortex. SPs recorded from the symmetrical sites of the two hemispheres showed no significant differences in amplitude and duration. Moreover, the SPs did not show significant differences in amplitude and distribution between two test models (R Model and B Model). The results obtained from the extinction experiments showed that after extinction of the behavioral responses the SPs disappeared. The results showed that the SPs recorded were learning-dependent and represented the association of events. As the SPs appeared in the delay period and were prefrontal-dominant, it was suggested that the prefrontal cortex might play an important role in short-term memory process.

Action Potentials

Configural associations in discrimination learning.

In 4 experiments, Sprague-Dawley rats and homing pigeons received training with an A+ AB0 BC+ discrimination, in which food (+) accompanied trials with A and BC. Food was not presented (0) on trials with the compound AB. Subsequent test trials revealed that responding during C by itself, or the compound ABC, was slower than during either A or BC. Responding during the ABC compound was also found to be slower after training with the A+ AB0 BC+ than an A0 AB+ BC+ discrimination. We argue that these findings demonstrate the importance of configural associations in discrimination learning. Two accounts for the way in which these associations exert their influence are considered.

Animals

Fornix damage enhances successive, but not simultaneous, object-discrimination learning in cats.

The purpose of this study was to compare the effects of fornix lesions with the deficits known to follow septum lesions in cats learning visual object discriminations. In Experiment 1 when eight cats with aspiration lesions of the fornix performed successive discrimination problems, acquisition was greatly facilitated, but first- and second-reversal scores were normal by comparison with eight normal cats and two operated corpus callosum-control cats without fornix damage. Four corpus callosum-damaged cats with secondary degeneration in the medial fornix also learned the initial problem faster than normals. In Experiment 2 in a simultaneous paradigm, eight cats with fornix lesions scored like five normal controls, although they perseverated in early stages of reversal problems. The authors hypothesize that medial fornix damage, in contrast with septum lesions, enhances both initiation and maintenance of response inhibition.

Afferent Pathways