Formation Of Stimulus-reward Associations Research Articles

Post-training depletions of basolateral amygdala serotonin fail to disrupt discrimination, retention, or reversal learning.

In goal-directed pursuits, the basolateral amygdala (BLA) is critical in learning about changes in the value of rewards. BLA-lesioned rats show enhanced reversal learning, a task employed to measure the flexibility of response to changes in reward. Similarly, there is a trend for enhanced discrimination learning, suggesting that BLA may modulate formation of stimulus-reward associations. There is a parallel literature on the importance of serotonin (5HT) in new stimulus-reward and reversal learning. Recent postulations implicate 5HT in learning from punishment. Whereas, dopaminergic involvement is critical in behavioral activation and reinforcement, 5HT may be most critical for aversive processing and behavioral inhibition, complementary cognitive processes. Given these findings, a 5HT-mediated mechanism in BLA may mediate the facilitated learning observed previously. The present study investigated the effects of selective 5HT lesions in BLA using 5,7-dihydroxytryptamine (5,7-DHT) vs. infusions of saline (Sham) on discrimination, retention, and deterministic reversal learning. Rats were required to reach an 85% correct pairwise discrimination and single reversal criterion prior to surgery. Postoperatively, rats were then tested on the (1) retention of the pretreatment discrimination pair, (2) discrimination of a novel pair, and (3) reversal learning performance. We found statistically comparable preoperative learning rates between groups, intact postoperative retention, and unaltered novel discrimination and reversal learning in 5,7-DHT rats. These findings suggest that 5HT in BLA is not required for formation and flexible adjustment of new stimulus-reward associations when the strategy to efficiently solve the task has already been learned. Given the complementary role of orbitofrontal cortex in reward learning and its interconnectivity with BLA, these findings add to the list of dissociable mechanisms for BLA and orbitofrontal cortex in reward learning.

Conditioned effects of heroin on proinflammatory mediators require the basolateral amygdala

Heroin administration alters the induction of nitric oxide, a molecule known to play a critical role in immune function. Previous research has shown that these alterations can be conditioned to environmental stimuli that have been associated with drug administration. Little is known about the brain areas that mediate these effects; however, the basolateral amygdala (BLA) has been implicated in the formation of stimulus-reward associations within models of drug abuse. The present study sought to determine whether inactivation of the BLA would alter heroin's conditioned effects on the expression of inducible nitric oxide synthase (iNOS) and the proinflammatory cytokines TNF-alpha and IL-1beta in the rat. The conditioning procedure involved repeated pairing of heroin with placement into a standard conditioning chamber. To test the conditioned response, animals were returned to the previously drug-paired environment 6 days after the final conditioning session. Prior to testing, animals received intra-BLA microinfusions of a mixture of the GABA agonists muscimol and baclofen. Following removal from the chambers on test day, all animals received subcutaneous lipopolysaccharide to induce systemic expression of iNOS, TNF-alpha and IL-1beta. Analyses using real-time RT-PCR indicated that inactivation of the BLA blocked the suppressive effect of heroin-associated environmental stimuli on iNOS induction and on the expression of the proinflammatory cytokines TNF-alpha and IL-1beta in spleen and liver tissue. This study is important because it is the first to demonstrate that heroin's conditioned effects on proinflammatory mediators require the BLA. These findings may have significant implications for the treatment of heroin users.

Preference formation and working memory in Parkinson's disease and normal ageing

Recent studies in rats have suggested that the amygdala and the dorsal striatum may be differentially involved in the formation of stimulus-reward associations and stimulus-response associations, respectively. In a recent study in humans, conditioned preference learning deficits were observed in a group of patients with damage to the amygdala formation. In this study, patients with Parkinson's disease, which is known to involve pathology of the dorsal striatum, were tested on the same conditioned preference task, together with a group of patients with circumscribed lesions of the frontal lobe. Unlike patients with frontal lobe damage, patients with Parkinson's disease did not exhibit conditioned preferences. However, in this respect their behaviour was indistinguishable from that of age-matched (older) control subjects. In keeping with previous literature, working memory deficits were observed in both patients with Parkinson's disease and patients with frontal-lobe lesions. Compared to young control subjects, a strong increase in preference for familiar, versus novel, items was observed in both patients with Parkinson's disease and in older control subjects. Such a familiarity effect appears to overshadow the conditioning manipulation employed in this task and, therefore, preclude the expression of conditioned preferences in older subjects. These results suggest that there is a developmental progression in the degree to which different mechanisms of ‘learning to like’ are important over the life span.

Recovery of associative function following early amygdala lesions in rats.

Adult rats with amygdala lesions made at either Postnatal Day (PND) 10 or PND40 were tested on a series of reversal tasks that tap the ability to form stimulus-reward associations. PND40 rats were significantly impaired relative to both controls and PND10 rats on learning rate of the original discrimination and subsequent reversals. Analyses of discrete learning phases revealed that the impairment was specific to the postchance phase. The PND10 group was not impaired relative to controls on any measure. These results confirm prior findings that amygdala lesions sustained in adulthood impair the formation of stimulus-reward associations. They also demonstrate that substantial sparing or recovery of function is possible when the lesion is made during early development. Furthermore, the findings support the view that behavioral recovery may be more likely if the lesion is sustained near the time of peak synaptogenesis.

Outflow from the nucleus accumbens to the pedunculopontine tegmental nucleus: A dissociation between locomotor activity and the acquisition of responding for conditioned reinforcement stimulated by d-amphetamine

Output of neuronal information from the nucleus accumbens to the ventral pallidum is known to be a critical pathway in the expression of locomotion and incentive-related behaviour. Some signals from this structure are relayed forward through the dorsomedial nucleus of the thalamus to the medial prefrontal cortex, but the other major pathway from this site is a descending innervation to the pedunculopontine tegmental nucleus. Information carried by these descending neurons has been linked with both the output of locomotor activity and incentive-related information. Previous studies carried out in this laboratory have shown no changes in locomotor activity-either spontaneous or in response to systemic administration of d-amphetamine or apomorphine—in rats with excitotoxic lesions of the pedunculopontine tegmental nucleus. The present experiments compare the effects of ibotenate lesions of this nucleus in tests of locomotor activity or the acquisition of responding with conditioned reinforcement, following injections of d-amphetamine directly into the nucleus accumbens. In general agreement with previous results, ibotenate lesions of the pedunculopontine tegmental nucleus did not alter locomotion stimulated directly from the nucleus accumbens. However, comparable lesions in a group of trained rats produced an array of deficits in the conditioned reinforcement paradigm. Most notably, these rats directed their attention almost entirely towards pressing the levers (practically ignoring the food-hopper panel), but did not appear to be able to discriminate between them, while controls focused almost all their efforts on pressing the reinforcing lever (virtually ignoring the non-reinforcing lever) and the food-hopper panel. These results indicate that pedunculopontine tegmental nucleus lesions disrupt an element of reward-related responding, but do not affect the production of locomotor activity. This highlights the unlikely existence of specific “locomotion-inducing” centres in the mesencephalon and implicates the pedunculopontine tegmental nucleus in the formation of stimulus-reward associations. These data are discussed with respect to a role for the pedunculopontine tegmental nucleus in response selection.

Amygdaloid complex lesions differentially affect retention of tasks using appetitive and aversive reinforcement.

The hypothesis that the amygdaloid complex (AC) is involved in the formation of stimulus-reward associations was examined. A series of experiments (1A-1C) directly compared the effects of lesions (produced by injection of the excitotoxin N-methyl-D-aspartic acid) on 1-trial appetitive and 1-trial aversive learning in rats. Experiments 1A and 1B, which used different degrees of reinforcement, revealed no effect of lesions on the appetitive task, whereas acquisition of the aversive task was significantly impaired. This impairment depended on the nature of the aversive reinforcement used: Impairment was seen when a highly aversive stimulus (footshock) was used but not when a less aversive stimulus (0.2% quinine solution) was used. Control experiments indicated that the effect of lesions was not due to reduced sensitivity to the foot-shock. In Experiment 2, a novel odor conditioning task examined further the effect of AC lesions on the acquisition of appetitive and aversive stimulus-reinforcement associations. As in Experiment 1, the AC lesions impaired learning of the aversive association but did not significantly influence the appetitive association. It is argued that, although the AC may be involved in some types of appetitively rewarded learning, the findings of a differential effect of AC lesions on aversively rewarded learning suggest a role in learning beyond the formation of stimulus-reinforcement associations.