Rats with basolateral amygdala lesions show normal increases in conditioned stimulus processing but reduced conditioned potentiation of eating

Rats with neurotoxic lesions of basolateral amygdala (ABL) and control rats showed comparable enhancement of attentional processing of a visual stimulus when its predictive value was altered. In contrast, lesioned rats showed less potentiation of eating than did control rats when food was available during presentations of a conditioned stimulus that was previously paired with food. When considered together with previous data, these results indicate a double dissociation between effects of lesions of the ABL and of the amygdala central nucleus on phenomena related to attentional processing and the acquisition of motivational value.     

Involvement of the amygdala in stimulus-reward associations: interaction with the ventral striatum

The involvement of the amygdala in the potentiation of responding for conditioned reinforcers following intra-accumbens amphetamine injections has been studied. Thirsty rats were trained to associate a light-noise compound stimulus with water and then implanted with guide cannulae in the nucleus accumbens. Half of these rats received excitotoxic lesions of the basolateral region of the amygdala by accumbens. Half of these rats received excitotoxic lesions of the basolateral region of the amygdala by infusing N-methyl-D-aspartate, whereas the other half received infusions of the vehicle. In the test phase, water was no longer presented but responding on one of two novel levers produced the light-noise compound (the conditioned reinforcer) whereas responding on the other lever had no effect. The two groups received four counterbalanced intra-accumbens infusions of amphetamine (3, 10 and 30 micrograms /microliter) or vehicle over four test days. Intra-accumbens amphetamine infusions dose-dependently increased responding on the lever providing a conditioned reinforcer but had no significant effect on responding on the lever which did not produce the conditioned reinforcer. Compared with controls, the lesioned group exhibited a significant, selective reduction in responding on the lever providing a conditioned reinforcer, with no change on the lever on which responding had no consequence, irrespective of drug or control treatment. Control experiments showed that the amygdala lesioned animals were not hypodipsic and exhibited similar levels of hyperactivity following intra-accumbens infusions of D-amphetamine. Furthermore, the capacity to discriminate the conditioned stimulus as well as to acquire a new motor task was not altered by the lesion. These results indicate a role for the amygdala in mediating the effects of stimulus-reward associations on behaviour, via an action on dopamine-dependent mechanisms of the ventral striatum.     

Taste-potentiated odor aversion learning: role of the amygdaloid basolateral complex and central nucleus.

The present study examined the relative contributions of the amygdaloid basolateral complex (ABL) and central nucleus (CN) to taste-potentiated odor aversion (TPOA) learning--an associative learning task that is dependent on information processing in two sensory modalities. In Experiment 1, rats with neurotoxic lesions of these systems were trained on the TPOA task by presenting a compound taste-odor conditioned stimulus, which was followed by LiCl administration. Results showed that ABL damage caused an impairment in potentiated odor aversion learning but no deficit in the conditioned taste aversion. In contrast, rats with CN damage learned both tasks. Experiment 2 examined the effects of ABL damage on TPOA and odor discrimination learning. The odor discrimination procedure used a place preference task to demonstrate normal processing of olfactory information. Results indicated that although ABL-lesioned animals were impaired on TPOA, there was no deficit in odor discrimination learning.     

Lesions of the nucleus accumbens in rats reduce opiate reward but do not alter context-specific opiate tolerance

Bilateral electrolytic lesions of the nucleus accumbens in rats eliminated the capacity of 10 mg/kg morphine to produce a conditioned place preference (Experiment 1). However, these lesions did not alter the capacity to establish context-specific tolerance to the analgesic effects of 5 mg/kg of morphine (Experiment 2). This latter finding indicates that rats with nucleus accumbens lesions are not impaired in associating the effects of morphine with a particular location. Thus, the failure of morphine to produce a conditioned place preference in these lesioned rats probably cannot be attributed to an inability to associate the effects of morphine with a particular chamber, i.e., the initially nonpreferred chamber. Rather, morphine may fail to establish a conditioned place preference in these rats because nucleus accumbens lesions disrupt a pathway that is critical in mediating the rewarding effects of opiates.     

Firing patterns of accumbal neurons during a pavlovian-conditioned approach task

The nucleus accumbens (NAc) is necessary for the expression of Pavlovian-conditioned approach behavior but not for the expression of instrumental behavior conditioned in sessions that set a low response requirement. Although numerous studies have characterized firing patterns of NAc neurons in relation to instrumental behavior, very little is known about how NAc neurons encode information in Pavlovian tasks. In the present study, recordings of accumbal firing patterns were made during sessions in which rats performed a Pavlovian-conditioned approach task. Most of the recorded neurons (74/83, 89%) exhibited significant responses during the conditioned stimulus (CS) presentation and/or the reward exposure. The reward responses were prevalent, predominantly inhibitory, and comparable to reward responses observed in various types of behavioral paradigms, including instrumental tasks. The CS responses could be segregated into multiple subtypes on the basis of directionality, onset latency, and duration. Several characteristics of the CS firing patterns were unique relative to cue responses observed previously during alternative types of conditioning sessions. It is possible that the novel firing patterns correspond to the differential contributions of the accumbens to Pavlovian-conditioned approach behavior and instrumentally conditioned behavior. Regardless, the novel patterns of firing add to existing evidence that characterization of accumbal firing patterns in Pavlovian tasks may provide additional information about the neurophysiological mechanisms that mediate accumbal contributions to behavior.     

Rat nucleus accumbens neurons predominantly respond to the outcome-related properties of conditioned stimuli rather than their behavioral-switching properties

It has been proposed that nucleus accumbens neurons respond to outcome (reward and punishment) and outcome-predictive information. Alternatively, it has been suggested that these neurons respond to salient stimuli, regardless of their outcome-predictive properties, to facilitate a switch in ongoing behavior. We recorded the activity of 82 single-nucleus accumbens neurons in thirsty rats responding within a modified go/no-go task. The task design allowed us to analyze whether neurons responded to conditioned stimuli that predicted rewarding (saccharin) or aversive (quinine) outcomes, and whether the neural responses correlated with behavioral switching. Approximately one third (28/82) of nucleus accumbens neurons exhibited 35 responses to conditioned stimuli. Over 2/3 of these responses encoded the nature of the upcoming rewarding (19/35) or aversive (5/35) outcome. No response was selective solely for the switching of the rat's behavior, although the activity of approximately one third of responses (11/35) predicted the upcoming outcome and was correlated with the presence or absence of a subsequent behavioral switch. Our data suggest a primary functional role for the nucleus accumbens in encoding outcome-predicting information and a more limited role in behavioral switching.     

Comparison of septal and fornical lesioned rats performance on the maier three table reasoning task

Neither septal nor fornix lesioned rats were able to successfully perform the Maier 3 table reasoning task. Detailed analysis of the performance patterns of both groups reveal a common feature of primary dependence on directional responses at the choice point. This response strategy, as opposed to the spatial strategy attributed to normal animals, does differentiate between the two lesion groups. Septal lesioned subject show a dependence on a preferred or dominant direction of turning at the choice point both within and over trials. Fornical lesioned animal demonstrate the same pattern but only over trials. In addition, fornical lesioned rats tend to continue responding even though they had successfully reached the goal table. It is argued that fornical lesioned rats may not be able to use spatial information while septal rats who evidence repetitive errors, made by alternating between environmental locations, may attempt to acquire and unsuccessfully use spatial information.     

Conditioned circling in rats: bilateral involvement of the mesotelencephalic dopamine system demonstrated following unilateral 6-hydroxydopamine lesions

High rates of conditioned circling have previously been associated with a bilateral augmentation of striatal dopamine metabolism. These results suggest that both striata subserve this response. The present experiment further assessed this possibility by determining the effects of unilateral 6-hydroxydopamine lesions of the mesotelencephalic dopamine system on conditioned circling. Rats were initially trained to circle in their preferred direction for water reinforcement. Upon establishment of this response, they received unilateral lesions at the level of the lateral hypothalamus either contralateral or ipsilateral to the reinforced direction of circling. Reinforced responding was virtually abolished in rats with contralateral lesions. In contrast, rats lesioned ipsilateral to the direction of reinforced circling exhibited only a 50% decrease in rate of reinforced responding. Non-reinforced responding was increased only in rats with contralaterally placed lesions. Following 5 postoperative test sessions, the experimental contingencies were reversed. 'Ipsilaterally lesioned' rats were now required to circle away from their lesion whereas 'contralaterally lesioned' rats had to turn towards their lesion. The 'Contralateral' group acquired the reversal, such that reinforced responding occurred more frequently than non-reinforced responding. However, reinforced rates of responding did not reach preoperative rates. Conversely, 'ipsilaterally lesioned' rats could not learn to turn contraversively and now made more non-reinforced than reinforced responses. These findings suggest that conditioned circling is mediated by a bilateral involvement of the mesotelencephalic dopaminergic systems. However, the specific role of each side appears to be dependent upon its relationship with the direction of circling emitted.     

Fos and glutamate AMPA receptor subunit coexpression associated with cue-elicited cocaine-seeking behavior in abstinent rats

Cocaine-associated cues acquire incentive motivational effects that manifest as craving in humans and cocaine-seeking behavior in rats. We have reported an increase in neuronal activation in rats, measured by Fos protein expression, in various limbic and cortical regions following exposure to cocaine-associated cues. This study examined whether the conditioned neuronal activation involves glutamate AMPA receptors by measuring coexpression of Fos and AMPA glutamate receptor subunits (GluR1, GluR2/3, or GluR4). Rats trained to self-administer cocaine subsequently underwent 22 days of abstinence, during which they were exposed daily to either the self-administration environment with presentations of the light/tone cues previously paired with cocaine infusions (Extinction group) or an alternate environment (No Extinction group). All rats were then tested for cocaine-seeking behavior (i.e. responses without cocaine reinforcement) and Fos and AMPA glutamate receptor subunits were measured postmortem using immunocytochemistry. The No Extinction group exhibited increases in cocaine-seeking behavior and Fos expression in limbic and cortical regions relative to the Extinction group. A large number of Fos immunoreactive cells coexpressed GluR1, GluR2/3, and GluR4, suggesting that an action of glutamate at AMPA receptors may in part drive cue-elicited Fos expression. Importantly, there was an increase in the percentage of cells colabeled with Fos and GluR1 in the anterior cingulate and nucleus accumbens shell and cells colabeled with Fos and GluR4 in the infralimbic cortex, suggesting that within these regions, a greater, and perhaps even different, population of AMPA receptor subunit-expressing neurons is activated in rats engaged in cocaine-seeking behavior.     

Dopamine agonists increase perseverative instrumental responses but do not restore habit formation in a rat model of Parkinsonism

Dopamine (DA) deafferentation of the dorsolateral striatum has been shown to prevent habit development, leaving instrumental behavior under action–outcome control that is persistently sensitive to modification of the motivational value of the reward. The present experiment further explored the basis of this dysfunction by examining the ability of intrastriatal DA agonist injections (D1 SKF 38393 or D2/D3 Quinpirole) during overtraining of a signaled instrumental task to restore habit formation in rats subjected to bilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway. Overtraining was followed by a test of goal sensitivity by satiety-specific devaluation of the reward. The results confirmed the impaired shift in performance from action to habit in control lesioned rats. However, lesioned rats repeatedly injected with quinpirole D2/D3 agonist showed an increase in non-rewarded instrumental responses (intertrials periods) during overtraining, suggesting the development of perseverative behavior. Following the procedure of devaluation, quinpirole D2/D3 agonist treatment, and to a lesser extent SKF 38393 D1 agonist, caused the persistence of sensitivity to reward devaluation, indicating clear goal-directed behavior despite extended training. This absence of restoration of habit formation by DA agonist treatment is discussed in the light of DA agonist effects in Parkinson patients.     

Reward-related neuronal activity during go-nogo task performance in primate orbitofrontal cortex

The orbitofrontal cortex appears to be involved in the control of voluntary, goal-directed behavior by motivational outcomes. This study investigated how orbitofrontal neurons process information about rewards in a task that depends on intact orbitofrontal functions. In a delayed go-nogo task, animals executed or withheld a reaching movement and obtained liquid or a conditioned sound as reinforcement. An initial instruction picture indicated the behavioral reaction to be performed (movement vs. nonmovement) and the reinforcer to be obtained (liquid vs. sound) after a subsequent trigger stimulus. We found task-related activations in 188 of 505 neurons in rostral orbitofrontal area 13, entire area 11, and lateral area 14. The principal task-related activations consisted of responses to instructions, activations preceding reinforcers, or responses to reinforcers. Most activations reflected the reinforcing event rather than other task components. Instruction responses occurred either in liquid- or sound-reinforced trials but rarely distinguished between movement and nonmovement reactions. These instruction responses reflected the predicted motivational outcome rather than the behavioral reaction necessary for obtaining that outcome. Activations preceding the reinforcer began slowly and terminated immediately after the reinforcer, even when the reinforcer occurred earlier or later than usually. These activations preceded usually the liquid reward but rarely the conditioned auditory reinforcer. The activations also preceded expected drops of liquid delivered outside the task, suggesting a primary appetitive rather than a task-reinforcing relationship that apparently was related to the expectation of reward. Responses after the reinforcer occurred in liquid- but rarely in sound-reinforced trials. Reward-preceding activations and reward responses were unrelated temporally to licking movements. Several neurons showed reward responses outside the task but instruction responses during the task, indicating a response transfer from primary reward to the reward-predicting instruction, possibly reflecting the temporal unpredictability of reward. In conclusion, orbitofrontal neurons report stimuli associated with reinforcers are concerned with the expectation of reward and detect reward delivery at trial end. These activities may contribute to the processing of reward information for the motivational control of goal-directed behavior.     

Effects of basolateral amygdala dopamine depletion on the nucleus accumbens and medial prefrontal cortical dopamine responses to stress

In vivo voltammetry was used to study the effects of basolateral amygdala dopamine depletion on stress-induced dopamine release in the nucleus accumbens and medial prefrontal cortex. Male Long-Evans rats received bilateral microinjections of 6-hydroxydopamine or vehicle into the basolateral amygdala. Changes in dopamine signal were monitored in the nucleus accumbens and in the right and left hemispheres of medial prefrontal cortex, in lesioned animals and shams. Animals were subjected to a physical stressor (tail pinch) and a species-typical threat (fox odour); each stressor was presented twice over four consecutive daily sessions. The results indicate that the nucleus accumbens dopamine responses to both stressors are significantly potentiated by dopamine-depleting lesions to basolateral amygdala. In contrast, while the dopamine stress response in the left medial prefrontal cortex did not differ between lesioned animals and shams, the right medial prefrontal cortical dopamine response to tail pinch, but not fox odour stress, was significantly attenuated in lesioned animals. Therefore, basolateral amygdala dopamine depletion had opposite effects on the nucleus accumbens and medial prefrontal cortical dopamine responses to stress, although the effect on the latter is lateralized to the right hemisphere in a stressor-specific manner. These data indicate that stress-induced activation of meso-amygdaloid dopamine exerts an inhibitory influence on the nucleus accumbens dopamine response to stress. They also suggest the possibility that meso-amygdaloid dopamine influences the nucleus accumbens dopamine response to stress indirectly by modulating stress-induced dopamine release in medial prefrontal cortex. These findings add to a growing body of evidence of a preferential involvement of right medial prefrontal cortical dopamine in a wide range of physiological responses to stress.     

The Effects of Motivational and Emotional Factors in Glutamate Release in the Nucleus Accumbens of the Rat Brain during Food Consumption

Studies on male Sprague–Dawley rats using intracerebral dialysis and high-performance liquid chromatography with electrochemical detection showed that consumption of food with an attractive taste was accompanied by decreases in glutamate levels in the intercellular space of the nucleus accumbens, whose depth and duration depended on food deprivation. It was only in deprived animals that food consumption in conditions of presentation of a conditioned sound signal previously combined with electrocutaneous stimulation of the paws led to increases in intercellular glutamate levels in this structure. Isolated presentation of the aversion-relevant conditioned stimulation did not elicit changes in intercellular glutamate levels. These data suggest cooperativity in the actions of motivational and emotional factors in controlling glutamate release into the intercellular space of the nucleus accumbens during food consumption.     

Persistence of classical conditioned heart rate after extensive lesions of the striatum in rats

The participation of the Corpus Striatum in the acquisition and maintenance of conditioned heart rate was determined. After a 25 min period of adaptation in a sound attenuated chamber 8 rats were presented with a single association of a sound (CS) and a nociceptive stimulus (US) applied to the paws, while electrocardiographic recordings were made. Twenty-four hours later the sole application of CS produced a significant increment in the heart rate. The same results were obtained in 8 rats that were previously electrolytically lesioned in the corpus striatum. In another 8 rats the electrolytic lesions were performed after the acquisition session. These rats also showed the increment in heart rate produced by the CS during the testing session. Finally, in 8 more rats in which the association of CS-US was inversed no conditioned response was obtained. The electrolytic lesions comprised several milimeters of the corpus striatum involving the anterior medial and posterior part and even extended to surrounding areas. Nevertheless the animals were able to acquire and retain the vegetative conditioned response.     

Effects of fimbria-fornix lesion on avoidance conditioning in the rat

Learning of a conditioned avoidance response (CAR) in the shuttle box was studied in rats with lesions in the fimbria-fornix region. Lesioned rats showed facilitation in the acquisition of the CAR, accompanied by a lowered level of freezing responses and a higher level of intertrial activity. At shorter CS-UCS intervals lesioned rats showed better performance than controls. When measured in an activity box, a statistically significant increase in the spontaneous activity of lesioned animals was found. No increase in activity was observed, however, when the lesioned animals were tested in a linear maze. No changes in emotionality were found.     

Conditioned reflex release of dopamine in the nucleus accumbens after disruption of the hippocampal formation in rats

Vital intracerebral microdialysis combined with HPLC with electrochemical detection was used to study changes in dopamine release in the nucleus accumbens during the development and realization of an emotional conditioned response in hooded rats with lesions to the hippocampal formation. These studies showed that one month after bilateral administration of ibotenic acid into the hippocampal formation, rats had weakened emotional responses to contextual stimuli. The process of development of the conditioned reflex was accompanied by higher-level and longer-lasting release of dopamine in the nucleus accumbens than in shamoperated rats. Dopamine release levels in the nucleus accumbens during realization of the conditioned reflex to contextual stimuli in rats with hippocampal lesions and sham-operated rats were identical. Laboratory for the Physiology of Higher Nervous Activity, I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, 199034 St. Petersburg, Russia. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 1-2, pp. 76–82, January–February, 1997.     

Changes in dopaminergic neurotransmission do not alter somatic or motivational opiate withdrawal-induced symptoms in rats

Opiate withdrawal has been correlated with decreased extracellular dopamine (DA) levels in the nucleus accumbens (NAC) of morphine-dependent rats. The authors tested the hypothesis that DA transmission plays a critical role in the induction of motivational and somatic withdrawal symptoms. First, the authors used a 6-hydroxydopamine-induced lesion of the NAC to chronically disrupt mesolimbic DA transmission. Second, global DA neurotransmission was acutely stimulated by the nonselective DA agonist (apomorphine) or inhibited by nonselective DA antagonists (droperidol or flupentixol). Morphine-dependent rats bearing 6-hydroxydopamine-induced lesions displayed naloxone-precipitated motivational and somatic withdrawal symptoms similar to those of sham-lesioned rats. Administration of apomorphine did not reduce naloxone-induced opiate withdrawal. Moreover, in total absence of naloxone, DA antagonists did not precipitate either conditioned place aversion or somatic abstinence signs in dependent rats. Taken together, these findings suggested that DA transmission is not critical for the induction of opiate withdrawal syndrome.     

Effects of bilateral lesions of the cerebellar interpositus nucleus on the conditioned forelimb flexion reflex in mice

Three groups of mice, unoperated controls, sham and lesioned, were submitted to an associative conditioning of forelimb flexion reflex (FFR). Light and tone constituted the conditioned stimulus (CS) paired with a forelimb electric shock, the unconditioned stimulus (UCS). The first two groups were able to acquire an appropriate conditioned response. In the third group, each animal received a bilateral lesion of the cerebellar interpositus nucleus (IN). The subjects of this group were unable to acquire the conditioning. When bilateral lesions of the IN were done after the acquisition, no effect of the lesions could be detected during retention test sessions 10 days after surgery, by comparison with sham controls. It is therefore concluded that the cerebellar interpositus nucleus is an essential part of the circuit for the acquisition of associative conditioning of the forelimb flexion response in mice, but not for the retention of this task. Moreover, no direct sensorimotor effect of the lesion on performance itself could be evoked.     

The amygdala and flavour preference conditioning: Crossed lesions and inactivation

Current studies examined whether temporary inactivation of the amygdala influenced the learning and/or expression of conditioned flavour preferences and whether interactions between the amygdala and the nucleus accumbens contribute to this learning. Experiments 1A and 1B examined temporary inactivation of the amygdala in rats, by the administration of muscimol through chronically implanted cannulae, given during acquisition and/or expression of flavour preferences based on a sucrose reinforcer. Despite differences in the number of training trials and control procedures, in both of Experiments 1A and 1B inactivation during training attenuated, but did not totally prevent, the acquisition of a preference for the CS+ (conditioned stimulus) flavour over the CS−. Inactivation during testing had no effect on the preference for the CS+. In Experiment 2A rats were given access to a CS+ flavour paired with fructose and a CS− flavour without fructose prior to testing the preference for the CS+ over the CS− in the absence of the reinforcer. In Experiment 2B the same rats were tested for their preference with another set of CS+ and CS− flavours and maltodextrin as the reinforcing solution. Contralateral unilateral lesions of the amygdala and nucleus accumbens attenuated, but did not totally prevent, flavour preference learning based on either fructose or maltodextrin compared to either ipsilateral or sham lesioned animals. These results suggest that the amygdala plays a role in the learning, but not expression, of flavour preferences and that this role is partially dependent on interactions with the nucleus accumbens.