Differential involvement of the basolateral amygdala, orbitofrontal cortex, and nucleus accumbens core in the acquisition and use of reward expectancies.

In this study, the authors tested the hypothesis that the basolateral amygdala (BLA), orbitofrontal cortex (OFC), nucleus accumbens core (NA-core), and the extended hippocampus mediate different aspects of the development-maintenance of unique reward expectancies produced by the differential outcomes procedure (DOP). Rats were trained with either DOP or a nondifferential outcomes procedure (NOP) on a simple discrimination task. Fornix lesions did not affect either version of the task, demonstrating that the extended hippocampal system has no role in stimulus-outcome (S-O) associations. In contrast, in the DOP condition, BLA lesions impaired performance throughout training, OFC lesions impaired choice accuracy only in the later maintenance phase, and NA-core lesions resulted in enhanced learning. These results suggest that BLA and OFC are important for establishment (BLA) and behavioral maintenance (OFC) of S-O associations, whereas the NA-core is not needed and can in fact impede using multiple S-O associations. No impairments were observed in the NOP condition, demonstrating that these structures are not critical to stimulus-response learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects on effort discounting induced by inactivations of the nucleus accumbens core or shell.

The authors investigated the contribution of the nucleus accumbens (NAc) core and shell to effort-based decision making using a discounting procedure. Selection of 1 lever delivered a smaller, 2-pellet reward immediately, whereas the other lever delivered a 4-pellet reward after a fixed ratio of presses (2, 5, 10, or 20) that increased over 4 blocks of 10 discrete choice trials. Subsequent testing employed an equivalent delays procedure, whereby the relative delay to reward delivery after selection of either option was equalized. In well-trained rats, inactivation of the core, but not the shell, via infusion of GABA A/B agonists muscimol/baclofen reduced preference for the high-effort option under standard conditions and also when rats were tested using an equivalent delays procedure. However, inactivation of the core did not alter preference for 4-pellet versus 2-pellet rewards when the relative costs of each option were the same (1 press). Thus, the NAc core, but not the shell, appears to be part of a neural circuit that biases choice toward larger rewards associated with a greater effort cost. Furthermore, the contributions by the NAc core to this form of decision making can be dissociated from its role in delay discounting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nucleus accumbens dopamine modulates response rate but not response timing in an interval timing task.

While previous work has demonstrated that systemic dopamine manipulations can modulate temporal perception by altering the speed of internal clock processes, the neural site of this modulation remains unclear. Based on recent research suggesting that changes in incentive salience can alter the perception of time, as well as work showing that nucleus accumbens (NAc) shell dopamine (DA) levels modulate the incentive salience of discriminative stimuli that predict instrumental outcomes, we assessed whether microinjections of DA agents into the NAc shell would impact temporal perception. Rats were trained on either a 10-s or 30-s temporal production procedure and received intra-NAc shell microinfusions of sulpiride, amphetamine, and saline. Results showed that NAc DA modulations had no effect on response timing, but intra-NAc shell sulpiride microinfusions significantly decreased response rates relative to saline and amphetamine. Our findings therefore suggest that neither NAc shell DA levels, nor the resultant changes in incentive salience signaled by this structure, impact temporal control. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Effects of reward timing information on cue associability are mediated by amygdala central nucleus.

The central nucleus of the amygdala (CeA) has been implicated in a range of associative learning phenomena often attributed to changes in attentional processing of events. Experiments using a number of behavioral tasks have shown that rats with lesions of CeA fail to show the enhancements of stimulus associability that are normally induced by the surprising omission of expected events. By contrast, in other tasks, rats with lesions of CeA show normal enhancements of associability when events are presented unexpectedly. In this experiment, we examined the effects of CeA lesions on changes in cue associability in a reward timing task. In sham-lesioned rats, the associability of cues that were followed by stimuli that provided reward timing information was maintained at higher levels than that of cues that were followed by uninformative stimuli. Rats with lesions of CeA failed to show this advantage. These results indicate that the role of CeA in the modulation of associability is not limited to cases of event omission. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Fos expression in the prefrontal cortex and nucleus accumbens following exposure to retrospective timing tasks.

The dorsal striatum and prefrontal cortex have been implicated in interval timing. We examined whether performance of temporal discrimination tasks is associated with increased neuronal activation in these areas, as revealed by Fos expression, a marker for neuronal activation. In Experiment 1, rats were trained on a discrete-trials temporal discrimination task in which a light (22 cd/m2) was presented for a variable time, t (2.5–47.5 s), after which levers A and B were presented. A response on lever A was reinforced if t t > 25 s. A second group was trained on a light-intensity discrimination procedure, in which a light of variable intensity, i (3.6–128.5 cd/m2) was presented for 25 s. A response on lever A was reinforced if i i > 22 cd/m2. In Experiment 2, bisection procedures were used to assess temporal (200–800 ms, 22 cd/m2) and light-intensity (3.6–128.5 cd/m2, 400 ms) discrimination. The increase in proportional choice of lever B as a function of stimulus duration or intensity conformed to a two-parameter logistic equation. Fos expression in the prefrontal cortex and nucleus accumbens was higher in rats performing temporal discrimination tasks than in those performing light-intensity discrimination tasks, indicating greater neuronal activation in these areas during temporal discrimination tasks. Fos expression in the dorsal striatum did not differ between rats performing temporal and light-intensity discrimination tasks. These results suggest that the prefrontal cortex and nucleus accumbens are involved in temporal discrimination. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

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)     

Real-time dopamine efflux in the nucleus accumbens core during Pavlovian conditioning.

To assess the role of dopamine input to the nucleus accumbens core in anticipatory learning, fast-scan cyclic voltammetry was combined with appetitive Pavlovian conditioning. One group of rats (Paired) received 16 tone-food pairings for at least four daily sessions while the control group (Unpaired) received the same number of unpaired tone and food presentations. Both groups showed transient dopamine responses during food presentation throughout training, confirming dopamine involvement in reward processing. Only the Paired Group, however, showed consistently timed dopamine transients during the 10-s tone presentation. Transients first appeared near the end of the tone period as each animal acquired the tone-food association and then occurred progressively sooner on subsequent sessions. Later sessions also revealed a consistently timed dopamine response soon after food delivery in Paired animals. Collectively, these results implicate phasic dopamine release in the acquisition of Pavlovian learning and also suggest an early dopamine response to the unconditioned stimulus as training continues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Muscarinic receptor antagonism of the nucleus accumbens core causes avoidance to flavor and spatial cues.

Pharmacological blockade of muscarinic receptors in the nucleus accumbens reduces food intake and instrumental behaviors that are reinforced by food delivery. Nucleus accumbens muscarinic antagonism may specifically suppress the hedonic or reinforcing effects of food, thus blocking its capacity to direct behavior. Alternatively, muscarinic receptor blockade may cause a negative hedonic state that interferes with appetitive learning and food intake. In these experiments, rats received infusions of scopolamine methyl bromide (10 μg/0.5 μl) into the nucleus accumbens core, following exposure to a novel flavor of liquid diet (Experiment 1) or prior to being placed into a place preference apparatus (Experiment 2). In both experiments, nucleus accumbens muscarinic receptor antagonism caused subsequent avoidance of the paired cue (flavor or spatial location). This effect was specific to cholinergic manipulation; no conditioned taste avoidance was observed after pairing the novel flavor with nucleus accumbens core antagonism of N-methyl-D-aspartate, dopamine D?, or opioid receptors (Experiment 3). These experiments confirm previous reports of a critical role for striatal acetylcholine in modulating goal-directed behaviors, but suggest caution when interpreting behavioral effects of pharmacological manipulation of striatal acetylcholine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrolytic lesions of the nucleus accumbens enhance locomotor sensitization to nicotine in rats.

Electrolytic lesions of the medial core of the nucleus accumbens (NAc) in male Long-Evans rats increased spontaneous locomotion, enhanced the locomotor stimulating effect of acute 5.0 mg/kg cocaine, enhanced the development and subsequent expression of locomotor sensitization produced by repeated injections of 0.4 mg/kg nicotine but not 7.5 mg/kg cocaine, and enhanced the expression of conditioned locomotion. Given that 6-hydroxydopamine lesions of the NAc typically have effects on locomotor-related processes that are opposite of those produced by electrolytic and excitotoxic lesions, these data are consistent with a hypothesis that the NAc output, especially from the core, inhibits a variety of such processes and that the DA input to the NAc enhances these processes by inhibiting this inhibitory output. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine exposure causes long-term increases in impulsive choice.

In this study, the authors examined the long-term effects of prior exposure to cocaine on a delay-discounting task commonly used to measure impulsive choice. Male Long-Evans rats received daily intraperitoneal injections of 30 mg/kg cocaine HCl or saline for 14 days. Following 3 weeks of withdrawal, rats began training. On each trial, rats were given a choice between 2 levers. A press on 1 lever resulted in immediate delivery of a single 45-mg food pellet, and a press on the other resulted in delivery of 4 pellets after a delay period. Impulsive choice was defined as preference for the small immediate over the large delayed reward. Three months after treatment, cocaine-exposed rats displayed increased impulsive choice behavior. They also showed less anticipatory responding (entries into the food trough) during the delays prior to reward delivery, indicating that the enhanced impulsive choice in these rats may be related to deficits in bridging the delay between response and reward. These data demonstrate that cocaine exposure can cause enduring increases in impulsive choice behavior, consistent with observations in human subjects with drug addictions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Laboratory and self-report assessments of impulsive behavior in adolescent daily smokers and nonsmokers.

This research compared adolescent daily smokers (n = 25) and nonsmokers (n = 26) on different measures of impulsivity. Assessments included question-based measures of delay (DDQ) and probability (PDQ) discounting, a measure of behavioral disinhibition (go-stop task), and a self-report measure of impulsivity (Barratt Impulsiveness Scale-Adolescent). Adolescent smokers were more impulsive on the DDQ and Barratt Impulsiveness Scale--Adolescent but not on the PDQ or the go-stop task. However, there was a significant interaction between smoking status and gender on the go-stop task, with male smokers performing less impulsively on this measure than male nonsmokers--an effect not observed with the female adolescents. These findings indicate that adolescents who smoke cigarettes are more impulsive with respect to some, but not all, types of impulsivity than are adolescents who do not smoke. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dimensions of impulsive behavior in adolescent smokers and nonsmokers.

Robust associations have been identified between impulsive personality characteristics and cigarette smoking during adolescents, indicating that impulsive behavior may play an important role in the initiation of cigarette smoking. The present study extended this research by using laboratory behavioral assessments to explore relationships between three specific dimensions of impulsive behavior (impulsive decision-making, inattention, and disinhibition) and adolescent cigarette smoking. Participants were male and female adolescent smokers (n = 50) and nonsmokers (n = 50). Adolescent smokers were more impulsive on a measure of decision-making; however, there were significant smoking status by gender interaction effects for impulsive inattention and disinhibition. Male smokers were most impulsive on the measure of inattention, but male smokers were least impulsive on the measure of disinhibition. Correlations between biomarkers of smoking and impulsive inattention and disinhibition were found for females but not males. The current findings, coupled with previous findings (Reynolds et al., 2007), indicate there may be robust gender difference in associations between certain types of impulsive behavior and cigarette smoking during adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The pedunculopontine tegmental nucleus and responding for sucrose reward.

Pedunculopontine tegmental nucleus (PPTg) lesions in rodents lead to increased sucrose consumption, but the psychological deficit behind this remains uncertain. To understand better the relationship between consumption of, and motivation for, sucrose, the authors trained rats to traverse a runway for 20% or 4% sucrose solution; after 7 days, concentrations were reversed. Control rats consumed more 20% than 4% sucrose solution and promptly altered run times in response to concentration change. PPTg-lesioned rats consumed normal quantities of 4% but more 20% sucrose solution than controls and took longer to alter their runway time following the concentration change. These data suggest that lesions of the PPTg do not alter motivation per se and might be better understood as inducing a response selection deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential involvement of nucleus accumbens shell and core subregions in maternal memory in postpartum female rats.

Maternal memory refers to the long-term retention of maternal responsiveness as a consequence of animals' prior experiences with their young. This study examined the relative roles of 2 subregions of the nucleus accumbens (NA; shell and core) in maternal memory in rats. NA shell lesions either before or immediately after a short experience significantly disrupted maternal memory, but lesions after a 24-hr maternal experience had no effect. NA core lesions had no significant impact on maternal memory. Cycloheximide (a protein synthesis inhibitor) at a high dose (25 μg/μl) infused in the NA shell immediately after 1 hr of maternal experience also significantly disrupted maternal memory, whereas infusions in the medial preoptic area had no effect. It was concluded that the NA shell, but not the NA core, is involved in the consolidation of maternal memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intracerebroventricular ethanol-induced conditioned place preferences are prevented by fluphenazine infusions into the nucleus accumbens of rats.

The rewarding properties of centrally administered ethanol (EtOH) were examined using a conditioned place preference (CPP) test. Male rats subjected to bilateral intracerebroventricular (icv) infusions of EtOH (0-240 nmol) produced a dose-dependent preference for the drug-paired environment that was potentiated by concurrent intravenous (iv) administration of heroin (0.025 mg/kg). The role of mesolimbic dopamine (DA) pathways in the development of EtOH reward was then examined by challenging EtOH-treated rats with bilateral intra-accumbens shell applications of a DA receptor antagonist. Fluphenazine (10 or 50 μg/side), infused immediately prior to daily place conditioning trials, was found to reliably attenuate the development of CPPs produced by icv EtOH administration. When fluphenazine was administered into the nucleus accumbens shell prior to the final test trial only (i.e., in already conditioned rats), intra-accumbens shell DA receptor blockade was found to prevent the expression of CPPs produced by icv EtOH. In summary, rats form reliable learned preferences for EtOH-paired locations (CPPs) that are potentiated by iv heroin and whose acquisition and expression rely on intact DA functionality within the nucleus accumbens. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disruption of Pavlovian contextual conditioning by excitotoxic lesions of the nucleus accumbens core.

Nucleus accumbens (NAcc) core lesions were performed either before or after Pavlovian aversive conditioning. NAcc core lesions had no effect on discrete-cue or contextual conditioned freezing during acquisition. During retention testing, neither pre- nor posttraining lesions had any effect on conditioned freezing to the discrete cue. However, pretraining lesions resulted in a profound impairment of contextual conditioned freezing in a retention test, and posttraining lesions resulted in a smaller impairment. NAcc core lesions had no effect on sensory or motor processes, as measured by shock reactivity and spontaneous locomotor activity. These results suggest that during acquisition, processes independent of the NAcc core mediate contextual conditioned freezing, but that the NAcc is implicated in the retention of this aversive memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amphetamine lowers brain stimulation reward (BSR) threshold in alcohol-preferring (P) and non-preferring (NP) rats: Regulation by D? and D? receptors in the nucleus accumbens.

Differences in the mesolimbic dopamine (DA) pathway that regulates alcohol preference may also increase sensitivity to the reinforcing effects of other drugs of abuse. In the present study, the curve-shift (rate-frequency) paradigm was used to quantify the interaction of amphetamine with the rewarding effects of lateral hypothalamic brain stimulation reward (BSR) in alcohol-preferring (P) and -nonpreferring (NP) rats. The role of D? and D? DA receptors of the nucleus accumbens (NAcc) in mediating the reward-potentiating effects of amphetamine was also determined. Animals were tested with randomly administered amphetamine (0.25, 0.75, 1.25 mg/kg ip), DA-receptor antagonists (SCH 23390 [2.0 μg, 5.0 μg]; eticlopride [2.0 μg, 5.0 μg]), or a combination of the 2 (SCH 23390 [2.0 μg, 5.0 μg] + 0.75 mg/kg amphetamine; eticlopride [2.0 μg, 5.0 μg] + 0.75 mg/kg amphetamine). Amphetamine produced comparable dose-related leftward shifts in the rate-frequency function for both P and NP rats, with a greater than 60% reduction observed in BSR threshold. On intervening days, baseline threshold was unaltered between tests and similar between rat lines. Unilateral infusion in the NAcc of either the D? or D? receptor antagonist produced rightward shifts in the rate-frequency function of amphetamine, completely reversing-attenuating its reward-enhancing effects. The results demonstrate that amphetamine produces similar threshold-lowering effects in both P and NP rats and that the reward-potentiating effects of amphetamine do not correlate with alcohol preference under the conditions of the present study. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A differential involvement of the shell and core subterritories of the nucleus accumbens of the rats in memory processes.

The role of the core and the shell subterritories of the nucleus accumbens in conditioned freezing and spatial learning was investigated by means of selective N-methyl-D-aspartate lesions. Shell-lesioned rats showed reduced conditioned freezing to context and a tendency toward reduced freezing to the discrete stimulus compared with controls. However, lesions of the core did not modify the freezing response either to the context or to the discrete stimuli. Although spatial memory, as assessed by a water-maze paradigm, was not disrupted by the lesions, in a 4-arm baited, 4-arm unbaited radial-arm maze paradigm, the shell-lesioned rats showed selective deficits in working memory, but not in reference memory. In contrast, core-lesioned rats showed no memory deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dimensions of impulsive behavior in adolescents: Laboratory behavioral assessments.

Impulsivity is a multifaceted construct that defines a range of maladaptive behavioral styles. The present research aimed to identify different dimensions of impulsive behavior in adolescents from a battery of laboratory behavioral assessments. In one analysis, correlations were examined between two self report and seven laboratory behavioral measures of impulsivity. The correlation between the two self report measures was high compared to correlations between the self report and laboratory behavioral measures. In a second analysis, a principal components analysis was performed with just the laboratory behavioral measures. Three behavioral dimensions were identified--"impulsive decision-making", "impulsive inattention", and "impulsive disinhibition". These dimensions were further evaluated using the same sample with a confirmatory factor analysis, which did support the hypothesis that these are significant and independent dimensions of impulsivity. This research indicates there are at least three separate subtypes of impulsive behavior when using laboratory behavioral assessments with adolescent participants. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation of appetitive Pavlovian conditioning by d-amphetamine in the shell, but not the core, of the nucleus accumbens.

The effects of postsession d-amphetamine within subregions of the ventral and dorsal striatum on appetitive Pavlovian learning were assessed. Rats acquired a conditioned approach response on presentation of a stimulus predictive of 10% sucrose solution (unconditioned stimulus [US]), but not during equally frequent presentations of a stimulus uncorrelated with the US. In Experiment 1, postsession d-amphetarnine infusions enhanced acquisition of conditioned responding, with no effect on control measures. In Experiment 2, rats received postsession d-amphetamine in the accumbens shell or core. Shell infusions facilitated conditioning; core infusions did not. In Experiment 3, dorsomedial striatal infusions of d-amphetamine also were ineffective. In sum, dopaminergic activation within the shell, but not the core, of the nucleus accumbens facilitates the acquisition of a Pavlovian association. (PsycINFO Database Record (c) 2010 APA, all rights reserved)