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Epinephrine facilitation of appetitive learning: attenuation with adrenergic receptor antagonists.

Previous studies using aversive training tasks have reported that retention is enhanced by post-training administration of epinephrine. This study investigated the effects of post-training administration of epinephrine on retention of an appetitive task. The results indicate that epinephrine can enhance retention performance in an appetitive task of both rats and mice. Pretraining injections of propranolol and phenoxybenzamine, alpha- and beta-adrenergic receptor antagonists, attenuate the memory-enhancing effects of epinephrine. These results are consistent with the view that release of peripheral epinephrine may regulate storage of new information and may mediate memory modulation produced by a variety of treatments.

Animals↗

Little oscillation of daily food intake in mousekiller rats as opposed to nonkiller rats before any confrontation with mice.

During 46 consecutive days the daily food intake and weight were recorded in 16 male Wistar rats. On Days 31-45 one mouse was presented each rat daily. Before any experience with mice (Days 0-27) the mousekiller rats, compared with the nonkiller rats, regulated their individual food intake more closely to their homeostatic equilibria, corrected for the linear trend. This result indicates a functional difference in food intake regulation between mousekiller rats and nonkiller rats prior to any experience with mice. However, no difference in the mean food intake was found between the mousekiller and the nonkiller rats.

Animals↗

Amnesia produced by anisomycin in an appetitive task is not due to conditioned aversion.

Two experiments investigated the effects of lithium chloride (LiCl) and anisomycin (ANI) in a water reward Y-maze task. In Experiment 1, male CD-1 mice given weak or strong training were injected post-training with either saline or LiCl (150 mg/kg), which has been reported to produce conditioned aversion in mice. One day after training, both LiCl groups avoided the rewarded arm of the maze and drank less water than saline-injected controls. Two days after training, the strongly trained LiCl mice showed avoidance, while both LiCl groups drank less water. In Experiment 2, weakly trained mice given pre- and post-training ANI (30 mg/kg) were amnesic on the second test day compared to mice that received post-trial saline. However, water consumption was increased on the test day for both groups. LiCl produced a different pattern of results than ANI in this task. On the basis of these results, it is suggested that amnesia produced by ANI is due to impaired memory formation and not to conditioned aversion.

Amnesia↗

Environmental variables and releasing-valence transfer in stimulus-directed pecking of chicks.

Releasing valence transfer occurs when the power or valence to release responses is transferred from a primary releasing stimulus to a second, initially neutral, stimulus. In the exemplar, pecking responses by neonatal chicks are released and directed by a pointed object operated to make pecking movements. Stimuli attached to or pecked by the arrow thereby acquire enhanced releasing valence. Chicks peck at matching stimuli in preference to comparable but unenhanced stimuli. Research reported here shows that primary and transferred releasing valences are differentially affected by environmental variables. Specific findings were Pecking by chicks occurs only within a narrow range of ambient temperature. Outside of this range, pecking is low in frequency and insensitive to valence-enhanced release. Pecking by chicks appears to be finely tuned to arrow peck rates between 120 and 180 pecks per minute. Within this range, frequency of pecks by chicks is low whereas the percentage of pecks to the valence-enhanced stimulus is maximal. The maternal food call was a weak releaser of pecking by chicks with no valence-enhancing properties.

Animals↗

Organization of rhythmic buccal motor output of Lymnaea stagnalis in the absence of food.

The pond snail Lymnaea stagnalis exhibits spontaneous rasping movements in the absence of food which are thought to be involved in food searching activity. Rasping activity is patterned into bouts, separated by periods of quiescence. Recordings from buccal feeding motoneurons in the isolated CNS reveal similar bouts of rhythmic motor output, though the modal cycle period is significantly longer than that shown by intact snails. Log survivorship curves of interval data from both intact animals and isolated CNS indicate that the pattern of motor output is controlled by at least two processes, one generating intervals between rasps within a bout, and the other generating intervals between bouts of rasping. When compared to well-fed individuals, 2-day-starved snails show significant enhancement of the probability function for generation of intervals between rasps within a bout; the function underlying between-bout intervals is not significantly affected.

Animals↗

The effects of p-chloroamphetamine, a depletor of brain serotonin, on the performance of rats in two types of positively reinforced complex spatial discrimination tasks.

Learning in male Sprague-Dawley rats was assessed in two types of positively reinforced complex spatial discrimination tasks (Stone 14-unit T-maze and eight-arm radial-arm maze) following cytotoxic lesions of central serotonergic terminal projection fields with p-chloroamphetamine (PCA). Learning, as expressed as mean number of errors per day and mean number of trails required to reach criterion, was significantly enhanced in the PCA-lesioned animals trained in the Stone maze. On the other hand, the performance of the PCA-lesioned animals trained in the eight-arm radial-arm maze was not found to differ significantly from that of saline-injected animals. The improved acquisition of the PCA-lesioned rats trained in the Stone maze was completely abolished following pretreatment with the selective serotonergic reuptake inhibitor norzimeldine. Neurochemical analyses of the brains of representative animals revealed that the levels of serotonin and its major metabolite, 5-hydroxy-3-indoleacetic acid, were both significantly reduced by PCA in all regions examined. While it is clear from these and other studies that the serotonergic nervous system plays an important role in the processes underlying learning and memory, these results further underscore the selective role of this neurotransmitter system in the way information is processed by the brain.

Amphetamines↗

Differential influences of corticotropin-releasing factor on memory retention of aversive learning and appetitive learning in rats.

The effects of intraamygdala injections of corticotropin-releasing factor (CRF) on memory retention of aversive and appetitive learnings were examined in the present study. Other than confirming the results of a previous study that a moderate dose of CRF (0.1 microgram) injected into the amygdala facilitated retention performance of an inhibitory avoidance task (electric shock punishment) 24 h after training, we have further found that this effect lasted for a week. However, CRF produced a differential dose-response effect upon memory of an appetitive learning paradigm (sexual reinforcement). CRF at 0.01 microgram enhanced retention at both 24-h and 1-week intervals, while CRF at 0.1 microgram impaired retention in the same task at 1 week only. These results confirm that the amygdala is important in memory processing and suggest that the mechanisms involved in the action of CRF on memory retention of aversive and appetitive learnings are different. The possible differences are also discussed.

Amygdala↗

Acute alcohol intoxication paired with appetitive reinforcement: effects upon ethanol intake in infant rats.

A recent study suggested that infant rats process alcohol odor and/or taste during acute ethanol intoxication probably due to ethanol elimination via respiration and salivation. The present set of experiments was meant to analyze the possibility that this orosensory processing may act as a conditioned stimulus when an appetitive reinforcer is paired with the state of intoxication. In the first experiment it was observed that intragastric administration of a mildly intoxicating ethanol dose (1.5 g/kg), paired during postabsorptive time intervals with oral infusion of sucrose, was sufficient to promote a significant preference to ethanol. In Experiment 2 different doses of ethanol were either paired or explicitly unpaired with sucrose administration. The result reported in Experiment 1 was replicated and it was observed that a higher dose (3.0 g/kg) unpaired with the reinforcer resulted in alcohol aversions in terms of alcohol consumption patterns. However, when the reinforcer was paired with this dose, the aversion was inhibited. Finally, in the third experiment results indicated that preexposure to alcohol odor eliminates sucrose-conditioned alcohol preferences. These results indicate that, in physiologically immature rats, alcohol preference can be regulated by prior associative experiences involving the state of intoxication and consequences internal and/or inherent to this state.

Alcohol Drinking↗

The failure of some rats to acquire intravenous cocaine self-administration is attributable to conditioned place aversion.

Although cocaine administration in humans includes euphoric and anxiogenic effects, the latter are less well understood. Acute cocaine administration produces aversive effects including anxiogenic effects as well as appetitive effects in rats and mice. In the present study the self-administration and conditioned place preference paradigms were used to determine whether the failure of some rats to acquire intravenous cocaine self-administration is attributable to either an interference with learning or an aversion to cocaine. Rats were classified as self-administrators or non-self-administrators based on the mean number of cocaine self-infusions per session and whether or not rats exhibited either a stable high level of responding or a stable low level of responding. Intravenously administered cocaine produced place preference for the self-administrators, while intravenously administered cocaine produced place aversion for the non-self-administrators. The fact that the non-self-administrators showed place aversion is inconsistent with the interpretation that the failure of these rats to readily self-administer is attributable to cocaine-mediated interference of learning. This is the first study in which both the self-administration and the conditioned place preference paradigms have been used in the same animals to demonstrate that the effects of cocaine are appetitive for some rats and aversive for others, and are not an artifact of cocaine's interference with learning.

Analysis of Variance↗

Defeat followed by individual housing results in long-term impaired reward- and cognition-related behaviours in rats.

In contrast to the well-documented acute effects on behavioural sensitivity, chronic effects that persist for weeks or even months after the cessation of the stressor received relatively little attention. This study aimed at the long-term effects of a severe stressor, i.e. social defeat followed by individual housing. Defeated and subsequently individually housed animals displayed impaired social memory, decreased social interaction and diminished anticipation for a sucrose solution for up until a period of 3 months after defeat. Remarkably, social housing counteracted the defeat-induced effects. The impaired capability to anticipate for a reward was discussed in relation to anhedonia, an important symptom of human depression. Moreover, the disturbed memory, the chronic nature of the effects, and the therapeutic effects of social housing, suggest that the defeat model may serve as a potential model for human psychopathology.

Analysis of Variance↗

Responsiveness to sucrose affects tactile and olfactory learning in preforaging honey bees of two genetic strains.

Using sucrose solution as reward, we conditioned preforaging honey bees of two genetic strains to tactile stimuli or to odours. Acquisition, extinction of conditioned responses and discrimination between the conditioned stimuli and alternative tactile or olfactory stimuli were measured. Bees of the two genetic strains were selected for their foraging behaviour. In addition, they differ in their responsiveness to sucrose. To analyse the effects of sucrose perception on learning parameters independent of foraging behaviour, we conditioned preforaging bees of the two strains and compared their performance in tactile and olfactory learning paradigms. In both strains, acquisition in tactile and olfactory conditioning is determined by responsiveness to sucrose. There is no genetic effect on the relationship between responsiveness to sucrose and acquisition. Bees responding to low sucrose concentrations perform better than ones that only respond to higher concentrations. Extinction of conditioned responses correlates with acquisition. Responses to alternative stimuli are independent of responsiveness to sucrose.

Animals↗

Role of 5-HT(1A) and 5-HT(7) receptors in the facilitatory response induced by 8-OH-DPAT on learning consolidation.

The present study further explored the mechanisms involved in the facilitatory effect induced by (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on learning consolidation. For this purpose, we analyzed in parallel the effects of LY215840 and ritanserin, two 5-HT(2) receptor antagonists with high affinity for the 5-HT(7) receptor, and WAY100635, a selective 5-HT(1A) receptor antagonist, on the facilitatory effect induced by 8-OH-DPAT on learning consolidation. We also determined whether LY215840 and/or ritanserin could be beneficial in restoring a deficient learning condition. Using the model of autoshaping task, post-training injection of LY215840 or WAY100635 had no effect on learning consolidation. However, both drugs abolished the enhancing effect of 8-OH-DPAT, with LY215840 being slightly more effective than WAY100635 in this respect. Ritanserin produced an increase in performance by itself and also abolished the effect of 8-OH-DPAT. Remarkably, selective blockade of 5-HT(2A) and 5-HT(2B/2C) receptors with MDL100907 and SB200646, respectively, failed to alter the 8-OH-DPAT effect. LY215840 and ritanserin, at the doses that inhibited the 8-OH-DPAT-induced response, reversed the learning deficits induced by scopolamine and dizocilpine. The present results suggest that the enhancing effect produced by 8-OH-DPAT on learning consolidation involves activation of 5-HT(1A) receptors and an additional mechanism, probably related to the 5-HT(7) receptor. Blockade of 5-HT(2) receptors, and perhaps of 5-HT(7) receptors as well, may provide some benefit in reversing learning deficits associated with decreased cholinergic and/or glutamatergic neurotransmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Elemental and configural visual discrimination learning following lesions to perirhinal cortex in the rat.

Rats were tested in a series of two-choice visual discrimination tasks in a computer-controlled testing apparatus. The discriminations used a range of discriminanda, which varied in complexity. The discriminations included relatively simple form discriminations, more complex form discriminations and discriminations between compound stimuli that shared many features. It was found that rats with perirhinal cortex lesions were unimpaired in all discriminations except those that involved the compound stimuli with overlapping features. Using these stimuli, rats with perirhinal cortex lesions were unimpaired when the stage of learning did not necessitate discriminating stimuli on the basis of more than one feature. However, when efficient performance of the task needed the configuration of more than one feature to be taken into account, perirhinal lesioned rats were impaired. These results are interpreted as revealing the role of the perirhinal cortex in providing multifeature information about the properties of visual objects.

Animals↗

Dead reckoning (path integration) requires the hippocampal formation: evidence from spontaneous exploration and spatial learning tasks in light (allothetic) and dark (idiothetic) tests.

Animals navigate using cues generated by their own movements (self-movement cues or idiothetic cues), as well as the cues they encounter in their environment (distal cues or allothetic cues). Animals use these cues to navigate in two different ways. When dead reckoning (deduced reckoning or path integration), they integrate self-movement cues over time to locate a present position or to return to a starting location. When piloting, they use allothetic cues as beacons, or they use the relational properties of allothetic cues to locate places in space. The neural structures involved in cue use and navigational strategies are still poorly understood, although considerable attention is directed toward the contributions of the hippocampal formation (hippocampus and associated pathways and structures, including the fimbria-fornix and the retrosplenial cortex). In the present study, using tests in allothetic and idiothetic paradigms, we present four lines of evidence to support the hypothesis that the hippocampal formation plays a central role in dead reckoning. (1) Control but not fimbria-fornix lesion rats can return to a novel refuge location in both light and dark (infrared) food carrying tasks. (2). Control but not fimbria-fornix lesion rats make periodic direct high velocity returns to a starting location in both light and dark exploratory tests. Control but not fimbria-fornix rats trained in the light to carry food from a fixed location to a refuge are able to maintain accurate outward and homebound trajectories when tested in the dark. (3). Control but not fimbria-fornix rats are able to correct an outward trajectory to a food source when the food source is moved when allothetic cues are present. These, tests of spontaneous exploration and foraging suggest a role for the hippocampal formation in dead reckoning.

Animals↗

Attentional set-shifting in mice: modification of a rat paradigm, and evidence for strain-dependent variation.

Increasingly precise molecular genetic tools are available to study in mice the cellular mechanisms underlying complex brain functions, but the behavioural paradigms to assess these functions often lack the required specificity. In this study, an attentional set-shifting paradigm to assess medial frontal cortex functions in rats was modified for use in mice and variation between two relevant mouse strains assessed. Male 129/SvEv and C57BL/6J mice and their F1 intercross (n=8 per genotype) were trained to dig in bowls for a food reward. On four consecutive days, mice performed a series of discriminations to criterion (six consecutive correct choices) between pairs of food bowls that differed along two dimensions (odour, digging medium), including a reversal, an intra-dimensional shift, and an extra-dimensional shift. Mice from the 129 strain performed significantly better than C57 mice in the initial acquisition of a simple discrimination and in the final extra-dimensional shift test, with no difference in the reversal and intra-dimensional shift. Performance of the F1 mice was intermediate or similar to that of the 129 mice. These results indicate a selective difference between these two strains in attentional selection processes that have been shown in humans, monkeys and rats to be mediated by prefrontal cortex.

Animals↗

Differences between appetitive and aversive reinforcement on reorientation in a spatial working memory task.

Tasks using appetitive reinforcers show that following disorientation rats use the shape of an arena to reorient, and cannot distinguish two geometrically similar corners to obtain a reward, despite the presence of a prominent visual cue that provides information to differentiate the two corners. Other studies show that disorientation impairs performance on certain appetitive, but not aversive, tasks. This study evaluated whether rats would make similar geometric errors in a working memory task that used aversive reinforcement. We hypothesized that in a task that used aversive reinforcement rats that were initially disoriented would not reorient by arena shape and thus make similar geometric errors. Tests were performed in a rectangular arena having one polarizing cue. In the appetitive condition water consumption was the reward. The aversive condition was a water maze task with reinforcement provided by escape to a hidden platform. In the aversive condition rats returned to the reinforced corner significantly more often than in the dry condition, and did not favor the diagonally opposite corner. Results show that rats can use cues besides arena shape to reorient in an aversive reinforcement condition. These findings may also reflect different strategies, with an escape/homing strategy in the wet condition and a foraging strategy in the dry condition.

Animals↗

Sulpiride alleviates the attentional impairments of rats with medial prefrontal cortex lesions.

Recent studies have shown that medial prefrontal cortex (mPFC) lesions impair performance on a number of rodent tests of attention. Although this evidence clearly suggests a role for the rat mPFC in attentional functions, it is unclear whether subcortical changes associated with mPFC lesions might also be relevant to the neuropsychological deficits observed. Given the ample evidence suggesting increased dopaminergic mechanisms in the basal ganglia following mPFC lesions, we investigated the effects of dopamine receptor agonists and antagonists on the attentional deficits associated with mPFC lesions. Rats trained on a five-choice reaction time task received either complete mPFC lesions or lesions restricted to its ventral subregions, the prelimbic and infralimbic cortices (PRL-IL). Compared with sham-operated rats, animals in both the lesioned groups were impaired at responding correctly to the visual targets, although this deficit was more marked in mPFC-lesioned rats. In addition, both lesions were associated with increased perseverative responding. The accuracy deficits of rats with mPFC lesions were alleviated by systemic administration of the dopamine D2 receptor antagonist sulpiride. In contrast, rats with PRL-IL damage were not affected and control rats were impaired by sulpiride. Administration of either the dopamine D1 receptor antagonist SCH 23390 or of pre-synaptic doses of apomorphine had similar, albeit non-significant effects. Higher doses of any of these drugs non-specifically impaired performance. These results extend previous findings of attentional impairments in rats with mPFC lesions and are compatible with recent hypotheses concerning the role of dopaminergic dysregulation in the pathogenesis of schizophrenia.

Animals↗

On the origins of autobiographical memory.

Tolving argues that one form of explicit memory, autobiographical memory is uniquely human and has no nonhuman animal antecedents. We suggest that a form of memory used by humans and nonhuman animals, dead reckoning, shares a common limbic structure, including the cingulate cortex and hippocampus, and involves similar processes in recognition of self-action. Thus, it may be homologous to, and an antecedent of, autobiographical memory in humans.

Animals↗