Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats.

The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an impaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS + significantly less often than controls, failing to discriminate between the CS + and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociable effects of cingulate and medial frontal cortex lesions on stimulus-reward learning using a novel Pavlovian autoshaping procedure for the rat: Implications for the neurobiology of emotion.

The effects of quinolinic acid-induced lesions of the anterior cingulate, posterior cingulate, and medial frontal cortices on stimulus-reward learning were investigated with a novel Pavlovian autoshaping procedure in an apparatus allowing for the automated presentation of computer-graphic stimuli to rats (T. J. Bussey, J. L. Muir, & T. W. Robbins, 1994). White vertical rectangles were presented on the left or the right of a computer screen. One of these conditioned stimuli (the CS+) was always followed by the presentation of a sucrose pellet; the other, the CS–, was never followed by reward. With training, rats came to approach the CS+ more often than the CS–. Anterior cingulate cortex-lesioned rats failed to demonstrate normal discriminated approach, making significantly more approaches to the CS– than did sham-operated controls. Medial frontal cortex-lesioned rats acquired the task normally but had longer overall approach latencies. Posterior cingulate cortex lesions did not affect acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulus Processing and Associative Learning in Wistar and WKHA Rats.

This study assessed basic learning and attention abilities in Wistar-Kyoto hyperactive (WKHA) rats using appetitive conditioning preparations. Two measures of conditioned responding to a visual stimulus, orienting behavior (rearing on the hind legs), and food cup behavior (placing the head inside the recessed food cup) were measured. In Experiment 1, simple conditioning, but not extinction, was impaired in WKHA rats compared with Wistar rats. In Experiment 2, nonreinforced presentations of the visual cue preceded the conditioning sessions. WKHA rats displayed less orienting behavior than Wistar rats but comparable levels of food cup behavior. These data suggest that WKHA rats exhibit specific abnormalities in attentional processing as well as in learning stimulus-reward relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bait-shyness acquisition is impaired by VMH lesions that produce obesity.

Lesioned Carworth CFE female rats in the area of the ventromedial nucleus of the hypothalamus (VMH) before or after avoidance learning. Prelesioned Ss learned to avoid familiar saccharin-sweetened water associated with apomorphine less rapidly, and during extinction lost the avoidance more rapidly than controls. Ss lesioned after avoidance learning continued to avoid, and during extinction lost the avoidance at the same rate as controls. When given ad-lib food and water, lesioned Ss became obese. 1 tentative interpretation is that VMH-lesioned rats overrespond to environmental stimuli, including their food. This interferes with gustatory-visceral associations needed for satiety and bait-shyness acquisition. Another possibility is that overresponding to environmental stimuli and impaired gustatory-visceral associations are both direct consequences of VMH lesions. (32 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A mathematical analysis on the biological zero problem in laser Doppler flowmetry

Whilst neurons within the lateral hypothalamus are well known to be responsive to the presentation of previously learned associative stimuli, the consolidation of a Pavlovian association is thought to depend in large part upon other brain regions, including the amygdala. The present study addressed this assumption directly, by examining the effect of post-session infusions of sulpiride within the lateral hypothalamus upon the acquisition of a conditioned approach response in an appetitive differential conditioning task. Subjects were exposed to an initially neutral stimulus (CS+), which immediately preceded the availability of a 10% sucrose reward (US). A second, control stimulus (CS ) was also presented. but never in close temporal proximity to the US. The number and duration of alcove approaches were recorded. Immediately following each training session, subjects were infused bilaterally with sulpiride (0, 0.5, 5 microg) in the vicinity of the perifornical region of the lateral hypothalamus. Sulpiride dose-dependently enhanced the rate of acquisition of a conditioned approach response to presentation of the CS+, but was without affect upon approach behaviour during CS(-) or US presentations. Thus, 0.5 microg sulpiride facilitated at an early stage (session 2 onwards) the number of alcove approaches to the CS+, while 5 microg sulpiride enhanced to a greater extent the duration of conditioned approach, particularly during later sessions. A subsequent locomotor test using 0.5 mg/kg d-amphetamine indicated that repeated infusions of the higher dose sulpiride (5 microg), but not the lower dose (0.5 microg), resulted in behavioural sensitisation to administration of the psychomotor stimulant. Acquisition of a novel conditioned instrumental response was not affected by previous exposure to sulpiride. These data suggest that dopamine-sensitive neurons within the lateral hypothalamus may play a significant role in the acquisition of appetitive Pavlovian associations.     

Triple dissociation of anterior cingulate, posterior cingulate, and medial frontal cortices on visual discrimination tasks using a touchscreen testing procedure for the rat.

Four experiments examined effects of quinolinic acid-induced lesions of the anterior cingulate, posterior cingulate, and medial frontal cortices on tests of visual discrimination learning, using a new "touchscreen" testing method for rats. Anterior cingulate cortex lesions impaired acquisition of an 8-pair concurrent discrimination task, whereas posterior cingulate cortex lesions facilitated learning but selectively impaired the late stages of acquisition of a visuospatial conditional discrimination. Medial frontal cortex lesions selectively impaired reversal learning when stimuli were difficult to discriminate; lesions of anterior and posterior cingulate cortex had no effect. These results suggest roles for the anterior cingulate, posterior cingulate, and medial frontal cortex in stimulus-reward learning, stimulus-response learning or response generation, and attention during learning, respectively. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Critical role of the parahippocampal region for paired-associate learning in rats.

Human amnesics are severely impaired in learning arbitrary associations between word pairs. This report examines the role of the hippocampal system in an analog of paired-associate learning developed for rats. Ss with selective damage to the parahippocampal region and controls were tested on an odor-guided paired-associate task. Normal rats readily learned to distinguish paired associates from various mispairings of the same odors, whereas most animals with parahippocampal damage failed to learn. Lesioned animals were, however, able to acquire correct responses to stimulus pairs for which an association between odors was not required. These findings extend the usefulness of olfactory learning as a model for studies of higher order learning capacity in rodents and indicate that in rats, as in humans, hippocampal areas are critical for learning arbitrary nonspatial relationships between stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Progressive ratio performance in rats with gustatory thalamus lesions.

To determine whether damage of the gustatory thalamus (the parvicellular region of the ventroposteromedial nucleus) disrupts the perceived value of reinforcing stimuli, the performance of rats with bilateral, electrophysiologically guided, electrolytic lesions of the area was examined in Experiment 1 with a progressive-ratio schedule of reinforcement. Lesioned rats showed normal concentration-dependent changes in break point (an index of the amount of effort a subject will expend to obtain reinforcement) and in consummatory responding (licking) for the sucrose reward. In the reward comparison procedure of Experiment 2, however, the same lesioned rats failed to show morphine-induced suppression of alanine consumption. The results provide no support for the view that the thalamic taste area is involved in the perception of the absolute reinforcing value of gustatory stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of the Impairment of Hippocampectomized Rats on the Radial-Arm Maze Cue Task by Visual Characteristics and Subicular Damage.

Rats with N-methyl-D-aspartate lesions of the hippocampus that partially damaged the subiculum and controls were trained on 2 versions of the radial-arm maze cue task, with either proximal or distal visual stimuli. In Experiment 1, the relative positions of the stimuli varied across trials. Lesioned rats were impaired when trained on the distal version, as opposed to transiently slowed down when trained on the proximal version. In Experiment 2, the relative positions of the stimuli were fixed throughout training. Lesioned rats were impaired when trained on the distal or the proximal version. Further analyses showed that combined damage to the hippocampus and the subiculum was required to impair performance in the proximal, but not the distal, version. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociation of Pavlovian and instrumental incentive learning under dopamine antagonists.

The administration of the dopamine antagonists, pimozide and α-flupenthixol, to rats reduced Pavlovian–instrumental transfer when a conditioned stimulus (CS) that had been paired with a noncontingent food reward was tested on instrumental performance. The administration of the antagonists during Pavlovian conditioning and/or testing abolished the enhancement of instrumental performance by the CS. The effect of both antagonists on instrumental incentive learning was then examined. After training in which the rats performed 2 responses for different food rewards, they consumed 1 type food under the antagonists and the other type under vehicle during reexposure. When instrumental responding was subsequently tested in extinction, performance was unaffected by whether the rats had been reexposed to the training reward under the antagonists. These results suggest that Pavlovian and instrumental incentive learning are not mediated by a common process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disruption of the connections between the mediodorsal and sulcal prefrontal cortices alters the associability of rewarding medial cortical stimulation to place and taste stimuli in rats.

This study involved 2 tests of conditioned reward with self-stimulation (SS) of the prefrontal cortex. In Experiment 1, rats were tested for a conditioned taste preference (CTP) induced by pairing a novel flavor with SS of the medial prefrontal cortex (MC). Normal rats displayed a CTP. Rats with bilateral cuts of the connections between the MC and sulcal prefrontal cortex (SC) did not show a CTP. In Experiment 2, similar cuts had no effect on the ability of SC SS to promote a CTP, showing that the cuts spare the ability to learn a CTP. In Experiment 3, rats were tested for a conditioned place preference (CPP) by pairing MC SS with environmental cues. Lesioned rats, but not intact rats, had a CPP. Results suggest the presence of prepotent relations, dependent on intrinsic prefrontal connections, between the rewarding effects of prefrontal stimulation and distinct sensorimotor domains. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of interference stimuli on the acquisition of learned aversions to foods in the rat.

Developed a learned food aversion paradigm to investigate characteristics of aversion learning likely to be involved in nutrient selection. The development of aversions to a relatively familiar, complete food was examined in 6 experiments with 186 Wistar-Furth rats with continuous access to that food. Learned food aversions were observed that were specific to the particular diet present during a sequence of toxic drug injections. Novel liquids and solids were also introduced in association with drug treatment to examine their effectiveness as interference stimuli. Flavored solutions, which have previously been reported to interfere with conditioned taste aversions, had little or no effect on learned aversions to the diet. This lack of interference by novel flavored liquids was coupled with significant conditioned aversions to the novel liquids themselves. Novel flavored solutions were contrasted with novel foods, which were extremely effective as interference stimuli in this paradigm. Possible bases for the observed differences in interference effects of foods and drinks are examined. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of basolateral and central amygdala differentiate conditioned cue preference learning with and without unreinforced preexposure.

In the separated arms conditioned cue preference (CCP) task rats are trained by confining them in one arm of an eight-arm radial maze with food and in another arm on the opposite side of the maze with no food on alternate days. After two such trials, rats prefer the food-paired arm when allowed to move freely between the two arms, neither of which contains food. However, if the rats are preexposed to the maze by exploring it without food before training, no preference is observed and at least 4 training trials are required to produce a CCP, suggesting that unreinforced preexposure to the maze latently inhibits acquisition. If this interpretation is correct, preexposure should reduce the size of the preference acquired with both 2 and 4 training trials. In Experiment 1, this prediction was replicated for 2 training trials; however, with 4 training trials, eliminating preexposure also eliminated the CCP. A previous finding that basolateral amygdala lesions impair the CCP with preexposure and 4 training trials was replicated in Experiment 2, but similar lesions had no effect on the CCP in nonpreexposed rats given 2 training trials. In contrast, lesions of the central nucleus impaired the 2 training trial CCP but had no effect on the 4 training trial CCP. This double dissociation suggests that the BLA-mediated 4 training trial CCP may be due to learning about the reward features of the maze space, while the central-nucleus-mediated 2 training trial CCP may be due to a conditioned approach response. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Conditioned facilitation of brain reward function after repeated cocaine administration.

Cocaine lowers brain reward thresholds, reflecting increased brain reward function. The authors investigated whether, similar to acute cocaine administration, cocaine-predictive conditioned stimuli would lower intracranial self-stimulation (ICSS) thresholds. Rats received a saline injection for 5 days, a cocaine injection (10 mg/kg) for 20 consecutive days, then saline for 5 additional days. Thresholds were measured immediately before and 10 min after each injection. The initial 5 saline injections had no effect on thresholds, whereas cocaine significantly lowered thresholds for 20 days. There was no tolerance or sensitization to this effect of cocaine over days. During the last 5 days when cocaine administration was substituted with saline, rats demonstrated a conditioned lowering of thresholds during the 2nd daily ICSS session. These data demonstrate that cocaine-predictive conditioned stimuli induce a conditioned facilitation of brain reward function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intraventricular Insulin and Leptin Reverse Place Preference Conditioned With High-Fat Diet in Rats.

The authors hypothesized that insulin and leptin, hormones that convey metabolic and energy balance status to the central nervous system (CNS), decrease the reward value of food, as assessed by conditioned place preference (CPP). CPP to high-fat diet was blocked in ad-lib fed rats given intraventricular insulin or leptin throughout training and test or acutely before the test. Insulin or leptin given only during the training period did not block CPP. Thus, elevated insulin and leptin do not prevent learning a food's reward value, but instead block its retrieval. Food-restricted rats receiving cerebrospinal fluid, insulin, or leptin had comparable CPPs. Results indicate that the CNS roles of insulin and leptin may include processes involving memory and reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of the retrosplenial cortex in processing multiple conditioned stimuli.

Lesions of retrosplenial cortex (RSP) disrupt spatial and contextual learning, suggesting that RSP may have a fundamental role in processing overlapping, or simultaneously presented stimuli. If so, then RSP lesions might also be expected to disrupt learning that requires the concurrent processing of phasic conditioned stimuli. In Experiment 1, rats were trained in a compound feature negative discrimination task in which a tone was presented and immediately followed by food on some trials, while on other trials a visual stimulus was simultaneously presented along with the tone and not reinforced. Normal rats learned to discriminate between the trials but RSP-lesioned rats exhibited low levels of conditioning on both types of trials. Experiment 2 demonstrated that this effect was not simply due to a general inability to form associations, since RSP-lesioned rats exhibited normal responding when the visual stimulus was presented alone and paired with food. These findings support the view that RSP has an important role in learning that involves the processing of simultaneously presented stimuli and have implications for understanding the functional relationship between the hippocampus and RSP. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of retrosplenial cortex in forming associations between multiple sensory stimuli.

The retrosplenial cortex (RSP) is highly interconnected with medial temporal lobe structures, yet relatively little is known about its specific contributions to learning and memory. One possibility is that RSP is involved in forming associations between multiple sensory stimuli. Indeed, damage to RSP disrupts learning about spatial or contextual cues and also impairs learning about co-occurring conditioned stimuli (CSs). Two experiments were conducted to test this notion more rigorously. In Experiment 1, rats were trained in a serial feature negative discrimination task consisting of reinforced presentations of a tone alone and nonreinforced serial presentations of a light followed by the tone. Thus, in contrast to prior studies, this paradigm involved serial presentation of conditioned stimuli (CS), rather than simultaneous presentation. Rats with damage to RSP failed to acquire the discrimination, indicating that RSP is required for forming associations between sensory stimuli regardless of whether they occur serially or simultaneously. In Experiment 2, a sensory preconditioning task was used to determine if RSP was necessary for forming associations between stimuli even in the absence of reinforcement. During the first phase of this procedure, one auditory stimulus was paired with a light while a second auditory stimulus was presented alone. In the next phase of training, the same light was paired with food. During the final phase of the procedure both auditory stimuli were presented alone during a single session. Control, but not RSP-lesioned rats, exhibited more food cup behavior following presentation of the auditory cue that was previously paired with light compared with the unpaired auditory stimulus, indicating that a stimulus-stimulus association was formed during the first phase of training. These results support the idea that RSP has a fundamental role in forming associations between environmental stimuli. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Simultaneous backward conditioned inhibition and mediated conditioning.

Demonstrations of retrospective revaluation suggest that remembered stimuli undergo a reduction in association with the unconditioned stimulus (US) present during learning. Conversely, demonstrations of mediated conditioning in flavor-conditioning experiments with rats suggest that remembered stimuli undergo an increase in association with the US present during learning. In a food allergy prediction task with 23 undergraduates, we demonstrated simultaneous backward conditioned inhibition and mediated conditioning effects. These results are compatible with the hypothesis that the direction of change (decrease or increase) in associative strength depends on whether the remembered stimulus was of a different category (conditioned stimulus/antecedent) or the same category (US/outcome) as the presented US. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The Mesocortical Dopamine Projection to Anterior Cingulate Cortex Plays No Role in Guiding Effort-Related Decisions.

Both mesolimbic dopamine (DA) and the anterior cingulate cortex (ACC) have been implicated in enabling animals to expend effort to obtain greater reward. To investigate the role of the DA pathway to ACC in working for reward, the authors tested rats on a cost-benefit T-maze paradigm in which they could either climb a barrier to obtain large reward in 1 arm (high reward [HR]) or select the low-effort alternative containing less reward (low reward [LR]). Surprisingly, ACC DA depletions had no effect on choice performance. Manipulations of barrier and reward sizes demonstrated that lesioned rats were as sensitive to the costs and benefits of the alternatives as controls. These results imply that the DA projection to ACC is not involved in guiding effort-related decisions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Operant and Pavlovian control of visual stimulus orienting and food-related behaviors in rats with lesions of the amygdala central nucleus.

The effects of superimposing operant reward and omission contingencies on 2 Pavlovian conditioned responses evoked by a visual conditioned stimulus paired with food were examined in rats with lesions of the amygdala central nucleus (CN). In sham-lesioned rats, the frequency of an orienting response, rearing, was increased by reward contingencies and decreased by omission contingencies, compared with yoked Pavlovian controls. In contrast, in CN-lesioned rats, rearing was not affected by either operant contingency and occurred at lower levels with Pavlovian procedures alone than in sham-lesioned rats. Nevertheless, CN-lesioned and sham-lesioned rats showed similar increases in the frequency of conditioned food-cup behavior with reward contingencies, similar decreases with omission contingencies, and similar levels of that response with Pavlovian procedures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)