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Gibson's invariance hypothesis and the Ames oscillatory effect.

Previous explanations of the Ames oscillatory effect are evaluated by means of a functional-evolutionary theory of perception. Use of stored interpretations, static elements, and other explanatory ideas are rejected in favor of adaptive response to ambiguity as the essential factor for the effect. It is emphasized that Ss report perception of rotation, oscillation, reversal, and flapping, which are all correlates of horizontal contraction and expansion of the retinal image, when viewing rotating objects. The provision of all possible correlates of the transforming array is described as supportive of a functional-evolutionary approach, and Gibson's theory of perception.

Animals↗

Tianeptine: 5-HT uptake sites and 5-HT(1-7) receptors modulate memory formation in an autoshaping Pavlovian/instrumental task.

Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the emerging notion that 5-HT plays a key role on memory formation.

Animals↗

Effects of priming stimulation of catecholamine containing nuclei in rat brain on runway performance.

Rats were implanted with bipolar fine wire stimulating electrodes in the region of the pontine nucleus locus coerulus (LC) and the pars compacta of the substantia nigra (SN). The reinforcing properties of stimulation of each electrode were determined. Subsequently, rats were run in a two alley runway and the effects of priming stimulation on performance in acquisition, discrimination and reversals were measured. It was found that LC priming caused an increased latency to exit from start box. Also, LC priming reduced running time in the rewarded alley in a reversal task whereas SN priming affected both performance in the rewarded and non-rewarded alley.

Animals↗

Cingulate cortical and anterior thalamic neuronal correlates of the overtraining reversal effect in rabbits.

Multiple-unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus in rabbits was recorded during reversal training, following differential conditioning of a locomotory (wheel rotation) avoidance response. The CS+ and CS- were pure tones (1 or 8 kHz) and the UCS was a footshock delivered through the grid floor of the wheel. One group of the rabbits received original training to a criterion followed immediately by reversal training. A second group received training to criterion followed by additional training sessions (overtraining), prior to reversal training. The results indicated that the overtraining reversal effect (ORE) occurred. That is, the overtrained subjects acquired the reverse discrimination in significantly fewer sessions than the non-overtrained subjects. The overall (non-discriminative) neuronal reactivity in all cingulate cortical laminae was reduced by overtraining, whereas the overall reactivity of the AV thalamus was enhanced. In addition, the non-overtrained subjects manifested a discriminative neuronal response appropriate to the original task (i.e. a greater response to the CS- than to the CS+ for reversal training), throughout the precriterial sessions of reversal training. This persistent 'original habit effect' occurred only at brief latencies (20-30 msec) after CS onset, and only in the deep cortical laminae (V-VI). The neuronal activity of the superficial laminae (I-IV) in non-overtrained subjects underwent a transition, in parallel with the behavior, from a discriminative response appropriate to the original task to one appropriate to the reversal task. No significant training-related changes were seen at any cortical depth in the overtrained subjects. Presentation of non-contingent footshocks during two sessions of reversal training following criterion re-enhanced the overall reactivity and the brief-latency discriminative neuronal response appropriate to the original task, which had undergone decline during reversal training, in the deep cortical laminae of the non-overtrained subjects. The enhanced overall reactivity and the discriminative activity in the superficial laminae of non-overtrained subjects had not declined during reversal training and were not altered by the non-contingent footshocks. The implications of these data are discussed in regard to the neural causation of the ORE.

Animals↗

Scopolamine disrupts visual reversal without affecting the first discrimination.

The effect of scopolamine (0.5 mg/kg) was determined in a brightness discrimination test (Y maze) motivated by electrical shocks (escape avoidance). Male adult Sprague Dawley rats were used. Results show that scopolamine impairs significantly the visual reversal without affecting the first brightness discrimination. The qualitative analysis reveals that the anticholinergic drug-induced deficit involves both perseveration, i.e. failure to suppress inappropriate response, and a tendency to adopt a position habit. A parallelism with hippocampal and frontal lobe damage symptoms is discussed and an interpretation in terms of disinhibition and incapacity to solve a more difficult problem is proposed.

Animals↗

Discriminative stimulus effects of nalbuphine in nontreated and morphine-treated pigeons.

In the present study, the stimulus effects of the low efficacy agonist nalbuphine were examined under two conditions: nontreated and morphine treated. In the first experiment, five pigeons were trained to discriminate among 3.2 mg/kg morphine, 5.6 mg/kg nalbuphine, and saline. Nalbuphine produced nalbuphine-like responding. Low doses of morphine produced nalbuphine-like responding, whereas high doses produced morphine-like responding. Naltrexone produced saline-like responding and reversed the stimulus effects produced by the training doses of morphine and nalbuphine. Five different pigeons were treated daily with 10 mg/kg morphine (i.m.) and trained 6 h later to discriminate among 10 mg/kg morphine, 1.0 mg/kg nalbuphine and saline. In these pigeons, morphine produced morphine-like responding and nalbuphine produced nalbuphine-like responding. Morphine abstinence produced nalbuphine-like responding that was reversed by morphine. Additionally, naltrexone produced nalbuphine-like responding. These data suggest that the discrimination between morphine and nalbuphine in the nontreated and morphine-treated pigeons may be based on the relative efficacy differences between morphine, a higher efficacy mu-agonist, and nalbuphine a lower efficacy mu-agonist.

Analgesics, Opioid↗

Perseverative effects of parabrachial lesions: a mechanism of reduced activation?

The acquisition of a spatial reversal task and two reversals of it and the acquisition of an active two-way avoidance task were tested in three groups of male Sprague-Dawley rats: two experimental and one control group. The experimental group received chemical lesions of the parabrachial nuclei (group NPB) or of the dorsal hippocampus (group HC), using ibotenic acid. (Ibotenic acid is a compound which, contrary to kainic acid, fails to produce distant lesions, but, in conformity with kainic acid, spares the majority if not all fibers of passage.) The control group (group CG) received injections of the vehicle solution only. Animals of group NPB, in comparison to those of the other two groups, acquired the reversal task more quickly, but in the acquisition of its two reversals they needed considerably more time and made more perseverative errors. Likewise, only group NPB was significantly impaired in the acquisition of the avoidance task. From these results and from available evidence on connections of the parabrachial neurons with regions specifically involved in variables of the tested tasks (such as the prefrontal cortex), it is concluded that the parabrachial region exerts an activating influence on forebrain areas.

Animals↗

Individual vocal recognition and the effect of partial lesions to HVc on discrimination, learning, and categorization of conspecific song in adult songbirds.

Among songbirds, the capacity to associate particular songs with particular singers (i.e., vocal recognition) forms the cognitive basis for more complex communication behaviors such as female choice and territoriality. In the present study, we combine operant conditioning techniques and excitotoxic lesions to the forebrain nucleus HVc to examine the role of this region in the discrimination, associative learning, and categorization of conspecific song. We trained adult male and female European starlings, Sturnus vulgaris, to recognize simultaneously the songs of several conspecific males. Then, using a series of transfer procedures, we demonstrate that correct recognition does not generalize to song bouts containing novel motifs from familiar singers. This suggests that starlings do not make use of individually invariant source or filter characteristics for vocal recognition. We then lesioned a portion of HVc bilaterally with ibotenic acid, and exposed the birds to a series of manipulations testing the discrimination, associative learning, and categorization of conspecific song. The lesions attenuated song production among males, but retention of the basic recognition task (i.e., maintenance of the discrimination) was unaffected. However, when the response contingencies were reversed-as a test of associative learning independent of discrimination-the initial performance and subsequent learning rate were negatively correlated with the size of the HVc lesions. This suggests that HVc plays a role in the formation of associations between a song and some referent. The results of this study are discussed in light of earlier claims regarding the role of HVc in the perceptual processing of conspecific song.

Acoustic Stimulation↗

Antidepressant-like effects of the subtype-selective nicotinic acetylcholine receptor agonist, SIB-1508Y, in the learned helplessness rat model of depression.

RATIONALE: Epidemiological studies of smokers suggest that there is a link between nicotine and depression. Nonetheless, few studies have examined the potential use of nicotinic ligands in the treatment of depression. OBJECTIVES: The goal of this study was to evaluate the effects of SIB-1508Y, a novel subtype-selective ligand for high affinity nicotinic acetylcholine receptors (nAChRs), in the learned helplessness model of depression in rats. METHODS: In this model, exposure to inescapable foot-shock produces a lasting deficit in escape responses emitted in a subsequent conditioned avoidance procedure (learned helplessness). The effect of SIB-1508Y on learned helplessness was compared to the clinically used antidepressants, imipramine and fluoxetine, and the non-selective nAChR ligand, nicotine. RESULTS: Similarly to imipramine and fluoxetine, subchronic treatment (5 days) with SIB-1508Y reversed the escape deficit in the learned helplessness model in a dose dependent manner. The effect of SIB-1508Y on learned helplessness was still apparent 1 week following drug administration and was also maintained after 4 weeks of daily administration. In contrast, while nicotine was able to attenuate the learned helplessness deficit, this trend only reached statistical significance after chronic administration. The non-competitive ion channel blocker mecamylamine increased escape failures when administered alone and blocked the effects of SIB-1508Y but not imipramine. SIB- 1508Y also produced an increase in avoidance responding, which suggests an enhancement of learning. CONCLUSION: These results not only suggest a role for nAChRs in the development of a depressive-like syndrome, but also that subtype-selective nAChR agonists, such as SIB-1508Y, may offer a novel therapeutic approach to the treatment of depression.

Animals↗

Individual aged rats are impaired on repeated reversal due to loss of different behavioral patterns.

Aged rodents compared to young rodents are impaired in making repeated reversals and more variable in performance on many tasks. In the present study, a comparison of ten aged (21 months) and 10 young (3 months) Sprague-Dawley rats on a repeated spatial discrimination reversal water escape task revealed that the deficient and variable performance of the aged rats was due to the aged animals developing deficits in different behavioral patterns that were necessary to perform the task. Individual aged rats had deficits in inhibiting an unlearned first choice tendency (perseveration), repeating a first choice that lead to escape on the preceding trial (win-stay deficit) or inhibiting a first choice that lead to confinement and delayed escape on the preceding trial (lose-shift deficit). Because the aged animals were deficient on one or more of the necessary behavioral processes, as a group they were deficient on the repeated reversal task. However, because the aged rats differed on the specific behavioral process(es) on which they were deficient, when evaluated on any one process they were more variable than were the younger rats.

Aging↗

Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats.

Previous studies indicate that diabetes mellitus might be accompanied by a certain erosion of brain function such as cognitive impairment. The aim of this study was to examine and compare the effects of melatonin and vitamin E on cognitive functions in diabetic rats. Diabetes was induced in male albino rats via intraperitoneal streptozotocin injection. Learning and memory behaviors were investigated using a spatial version of the Morris water maze test. The levels of lipid peroxidation and glutathione were detected in hippocampus and frontal cortex. The diabetic rats developed significant impairment in learning and memory behaviors as indicated by the deficits in water maze tests as compared to control rats. Furthermore, lipid peroxidation levels increased and glutathione concentration decreased in diabetic rats. Treatment with melatonin and vitamin E significantly ameliorated learning and memory performance. Furthermore, both antioxidants reversed lipid peroxidation and glutathione levels toward their control values. These results suggest that oxidative stress may contribute to learning and memory deficits in diabetes and further suggest that antioxidant melatonin and vitamin E can improve cognitive impairment in streptozotocin-induced diabetes.

Animals↗

Learning and memory impairment in cocaine-dependent and comorbid schizophrenic patients.

Impairments in verbal learning and memory functioning have been found to be cardinal features among individuals with schizophrenia as well as among non-schizophrenic cocaine abusers. Cognitive deficits in these areas, moreover, have been associated with poor treatment response and short-term outcome. Little is known, however, about the acute effects of cocaine abuse on schizophrenic patients' learning and memory functioning. Consequently, a potentially reversible and treatable source of cognitive impairment has been virtually ignored. The present study examined the extent of verbal learning and memory impairment in a group of cocaine-dependent schizophrenic patients (n=42) and a group of non-schizophrenic cocaine-dependent patients (n=21) within 72 h of the last cocaine use using the California Verbal Learning Test (CVLT). Schizophrenic patients (n=34) without any substance-use disorders were also tested in an identical time frame and served as a comparison group. Results revealed that all groups demonstrated significant learning and memory impairment relative to CVLT published age and gender corrected norms. Both cocaine-dependent and non-substance abusing schizophrenic groups presented a very similar pattern of impaired learning and recall performance across all CVLT task domains. Comorbid patients, in contrast, presented with marked deficits in their ability to learn and recall verbal information relative to either schizophrenic or cocaine-only groups. Moreover, the cocaine-abusing schizophrenic patients showed significant forgetfulness of the information that they did acquire during delayed recall conditions. The performance deficits exhibited by cocaine-abusing schizophrenic patients differed not only in relative severity of impairment, but also qualitatively in their increased rates of forgetfulness of acquired information. These results are interpreted in terms of the neurobiological substrates of learning and memory and the neurobiological impact of cocaine on schizophrenic patients' cognition during the early phase of inpatient hospitalization. These results suggest that comorbid patients should be targeted for specialized remediation efforts at the beginning phases of inpatient treatment.

Acute Disease↗

Sensitive periods for lead-induced behavioral impairment (nonspatial discrimination reversal) in monkeys.

A total of 52 nursery-reared monkeys (Macaca fascicularis) were dosed orally with 1.5 mg/kg/day of lead on one of four dosing regimens (13 monkeys/group): Group 1, vehicle only; Group 2, dosed with lead continuously from birth; Group 3, dosed with lead from birth to 400 days of age and vehicle thereafter; and Group 4, dosed with vehicle from birth to 300 days of age and lead thereafter. This dosing regimen allowed evaluation of differential infant vulnerability as well as reversibility of the behavioral toxicity of lead. Blood lead concentrations averaged 3-6 micrograms/dl when monkeys were not being exposed to lead, 32-36 micrograms/dl when being dosed with lead and having access to infant formula, and 19-26 micrograms/dl during lead exposure after weaning from infant formula. When monkeys were 5-6 years old, they were tested on a series of nonspatial discrimination reversal tasks: form, form with irrelevant color cues, color with irrelevant form cues, and alternating form and color. Group 2 exhibited the greatest degree of impairment compared to controls. Group 4 also exhibited impaired performance, although less marked than that of Group 2. Group 3 was not impaired on this series of tasks. These results confirm findings observed in other monkeys exposed continuously to lead and suggest that while exposure beginning after infancy produces impairment, exposure during infancy as well exacerbates the effect.

Aging↗

Influence of MSH and corticosterone on stimulus control over an operant response.

Several previous papers have indicated that MSH/ACTH-like neuropeptides facilitate the reversal of brightness discrimination in a runway task. The present experiment was undertaken to explore the development during both acquisition and reversal of stimulus control over an operant response. Male albino adult rats were treated daily with either 10 micrograms of MSH, 500 micrograms of corticosterone or a placebo in a double blind procedure during the establishment of an on-light control over availability of reinforcement. Having completed this regime the conditions were reversed so that reinforcement was present only when the chamber-light was off. The results indicated that treatment with MSH during acquisition produced a significant decrease in % correct responses compared to animals treated with either the placebo or corticosterone with neither of these latter groups differing from the other. During the reversal phase of training there was a trend for both MSH and corticosterone to lower % correct responses. The discussion focuses on other literature which has shown opposite effects of corticosterone on aversive and appetitively motivated tasks.

Animals↗

Effects of methaqualone on learning: a failure to observe tolerance.

The study was designed to assess the effects of Methaqualone (MTQ) on learning, as well as the effects of 15 days of pretask drug exposure on performance. Forty CFE rats were randomly divided into four groups: Group I received daily IP injections of MTQ for 15 days prior to and throughout the duration of the task; Group II served as a control for Group I, receiving injections of the carrier vehicle; Group III received MTO at the start and throughout the duration of the task; Group IV served as the control for Group III. The task consisted of two pretraining days of swimming down a straight, all-white alleyway, followed by 5 trials/day for 4 days on a black-white discrimination task in a water T maze, with the white side being reinforced for all animals. Analyses revealed that MTQ animals made significantly more errors than controls. Pretask drug exposure did not significantly alter Group I performance versus Group III. Furthermore, continued injections for half of the animals in Group I and II for eight days following the last learning day did not improve Group I performance when retested on the same task. Thus MTQ adversely affected learning with prolonged drug exposure failing to reverse such debilitation.

Analysis of Variance↗

Acquisition and reversal of taste/tactile discrimination after forebrain noradrenaline depletion.

Two experiments were performed to assess the role of noradrenaline (NA) on the acquisition of an aversively motivated discrimination task and its reversal. A conditioned taste aversion procedure was used. The NA depletions were achieved through two different pharmacological means: systemic N-2-chloroethyl-N-ethyl-2-bromo-benzylamine (DSP4) and destruction of the dorsal noradrenergic bundle (DNAB) with 6-hydroxydopamine. Both procedures caused marked reductions of NA in the frontal cortex and hippocampus. In neither of the studies (Experiment 1, DSP4, and in Experiment 2, DNAB) were there any significant changes between controls and NA-depleted rats in either the rate of acquisition of the original discrimination (Phase 1) or the subsequent reversal (Phase 2). This occurred irrespective of which of the two stimuli (a taste cue, i.e., saccharin presented in bottles with nozzles that do not have ball bearings, "silent bottles," or a tongue-tactile cue, i.e., water in bottles with nozzles that had ball bearings "noisy bottles") initially was used as the conditioned stimulus (CS1, i.e., the stimulus first followed by contingent administration of lithium chloride, and later, in Phase 2, followed by saline injections). Thus NA does not appear to be critically involved in the acquisition and reversal of a taste/tactile discrimination task. The significance of forebrain NA for other discrimination tasks is discussed.

Animals↗

Phenylketonuria: enduring behavioral deficits in phenylketonuric rats.

The behavioral deficit in rats made "phenylketonuric" by ingestion of L-phenylalanine was evaluated 23 to 65 days following cessation of treatment. Animals treated from birth to 60 days showed significant deficit on reasoning and discrimination learning tests but not on discrimination reversal sets. Animals treated from 30 to 60 days showed significant deficit only on the reasoning test.

Animals↗

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