Progressive Ratio Task Research Articles

Link Between Increased Satiety Gut Hormones and Reduced Food Reward After Gastric Bypass Surgery for Obesity.

Context:Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms.Objective:To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression.Design:These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies.Patients:Two groups, more than 5 months after RYGB for obesity (n = 7–11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies.Intervention:Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task.Main Outcome Measures:Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups.Results:Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1.Conclusions:Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food.

Weight suppression in bulimia nervosa: Associations with biology and behavior.

Bulimia nervosa (BN) is a serious eating disorder that can persist for years and contribute to medical complications and increased mortality, underscoring the need to better understand factors maintaining this disorder. Higher levels of weight suppression (WS) have been found to predict both the onset and maintenance of BN; however, no studies have examined mechanisms that may account for the effects of WS on BN. We hypothesized that high WS would lead to reduced leptin levels, which may increase risk of binge eating by modulating reward responses to food. The current study examined the relationship between WS, leptin levels, and the reinforcing value of food in women with BN (n = 32) and noneating disorder controls (n = 30). Participants provided information on WS, completed a fasting blood draw to obtain serum leptin, and completed a progressive ratio task to measure the reinforcing value of food. Individuals with BN had greater WS (p < .01) and reinforcing food value (p < .05) compared with controls. Additionally, higher WS was associated with both lower leptin (p < .05) and increased reinforcing value of food (p < .05). Contrary to hypotheses, BN and control participants did not differ on leptin levels, and leptin levels were not significantly associated with the reinforcing value of food. Findings support that efforts to conform to the thin ideal may alter drive to consume rewarding foods and leave women vulnerable to binge episodes. However, mechanisms through which WS contributes to food reward and binge eating remain unknown.

The impact of social context on cigarette self-administration in nondependent smokers.

Tobacco use in nondependent smokers (i.e. chippers) is believed to be largely determined by situational factors including social context. However, little empirical research has examined how different social contexts impact chippers' smoking behaviour. Twenty-eight (16 men) chippers completed two laboratory sessions where they were offered an opportunity to self-administer puffs of their preferred tobacco brand using a progressive ratio task. During an individual session, participants self-administered cigarettes alone and during a paired session, they self-administered cigarettes with a coparticipant who was also smoking. The strongest predictors for number of self-administered puffs and breakpoint during the paired session were coparticipants' number of puffs and breakpoint, respectively (P<0.001), followed by puffs taken and breakpoint during the individual session (P<0.01). Current smoking frequency (cigarettes/week) did not significantly predict puffs taken or breakpoint during the paired session. Latency to cigarette self-administration during the paired session was correlated positively with coparticipants' latency (P<0.05), but not with latency during the individual session or cigarettes per week. The findings suggest that the presence of another smoker exerts an important influence on the quantity of chippers' smoking behaviour, such that chippers match their smoking behaviour to that of other smokers in their proximate environment.

Motivational assessment of mice using the touchscreen operant testing system: effects of dopaminergic drugs.

RationaleTouchscreens are widely used to examine rodent cognition. Current paradigms require animals to view stimuli and nose poke at an appropriate touchscreen location. After responding, there is little screen interaction and, as infra-red touchscreens eliminate the need for physical contact, minimal somatosensory feedback. It is therefore unclear if touchscreens can support the vigorous, repetitive responding required in paradigms like progressive ratio (PR) for assessing motivation and effort-related choice (ERC) for assessing decision-making.ObjectivesThis study aims to adapt and validate PR and ERC for the rodent touchscreen.MethodsMale C57Bl/6 mice were trained until responding on PR stabilised. Amphetamine, sulpiride and raclopride were administered via the intraperitoneal route to modify performance. Mice were transferred to ERC and paradigm parameters adjusted to demonstrate behavioural modification. ERC reward preference was assessed by home cage choice analysis.ResultsPR performance stabilised within seven sessions. Amphetamine (1 mg/kg) increased and raclopride (0.3 mg/kg) decreased performance by 63 and 28 %, respectively, with a 20-min injection-test interval. Sulpiride (50 mg/kg) decreased performance by 19 % following a 40-min injection-test interval. Increasing ERC operant requirements shifted responding from the operant response-dependent preferred reward towards the freely available alternative.ConclusionsVigorous, repetitive responding is sustainable in touchscreen PR and ERC and task validation mirrors non-touchscreen versions. Thus, motivation and reward-related decision-making can be measured directly with touchscreens and can be evaluated prior to cognitive testing in the same apparatus to avoid confounding by motivational factors.

Gastric bypass in rats does not decrease appetitive behavior towards sweet or fatty fluids despite blunting preferential intake of sugar and fat

After Roux-en-Y gastric bypass (RYGB) surgery, patients report consuming fewer fatty and dessert-like foods, and rats display blunted sugar and fat preferences. Here we used a progressive ratio (PR) task in our rat model to explicitly test whether RYGB decreases the willingness of rats to work for very small amounts of preferred sugar- and/or fat-containing fluids. In each of two studies, two groups of rats – one maintained on a high-fat diet (HFD) and standard chow (CHOW) and one given CHOW alone – were trained while water-deprived to work for water or either Ensure or 1.0M sucrose on increasingly difficult operant schedules. When tested before surgery while nondeprived, HFD rats had lower PR breakpoints (number of operant responses in the last reinforced ratio) for sucrose, but not for Ensure, than CHOW rats. After surgery, at no time did rats given RYGB show lower breakpoints than SHAM rats for Ensure, sucrose, or when 5% Intralipid served postoperatively as the reinforcer. Nevertheless, RYGB rats showed blunted preferences for these caloric fluids versus water in 2-bottle preference tests. Importantly, although the Intralipid and sucrose preferences of RYGB rats decreased further over time, subsequent breakpoints for them were not significantly impacted. Collectively, these data suggest that the observed lower preferences for normally palatable fluids after RYGB in rats may reflect a learned adjustment to altered postingestive feedback rather than a dampening of the reinforcing taste characteristics of such stimuli as measured by the PR task in which postingestive stimulation is negligible.

Effects of yohimbine and hydrocortisone pretreatment on opioid seeking, stress biomarkers and learning in heroin-dependent volunteers

Aims: Determine whether mu-opioid seeking, stress-related biomarkers, and associative learning are altered by manipulation of noradrenergic and glucocorticoid neurotransmission in heroindependent individuals. Methods: Subjects are being evaluated under buprenorphinemaintained, inpatient conditions using a 3×3 within-subject, randomized crossover, placebo-controlled, double-blind design. In each test session, oral pretreatment doses of the alpha2-adrenergic antagonist yohimbine (YOH 0, 27, 54mg) and glucocorticoid agonist hydrocortisone (CORT 0, 20, 40mg) are administered before a hydromorphone (HYD 1.5mg unit) vs. money ($2 unit) choice, progressive ratio task. Periodic measures include stress biomarkers (blood pressure, saliva cortisol and alpha-amylase), negative mood state, and hippocampal dependent (visual associative) learning measures. Results: In interim analyses (n=6 completers of 15 planned), YOH dose dependently increases HYD breakpoint (lin. F[1,5] = 6.37, p= .053), especially during CORT 40mg (lin. YOH×quadr. CORT F[1,5] = 10.77, p< .03). YOH dose dependently increases systolic and diastolic BP (lin. Fs[1,5] = 41.26 and 31.50, ps < .005); POMS Anxiety (lin. F[2,8]) = 2.71, p= .15; and associative learning rate (lin. F[1,5] = 6.11, p< .06), more so during placebo CORT (lin. YOH×quadratic CORT F[1,5] = 9.31, p< .03). YOH 27mg but not 54mg, relative to placebo, tends to increase cortisol (quadr. F[1,5] = 5.00, p<.08) but not alpha-amylase. CORT dose dependently increases cortisol (lin. F[1,5] = 32.20, p< .002) and decreases learning rate (lin. F[1,5] = 10.42,p< .03), but is not alteringother response measures. Conclusions: YOH-potentiated opioid seeking, blood pressure, and anxiety responses are consistent with Greenwald et al. (2013); emerging effects of YOH on cortisol and learning measures further validate this paradigm and extend findings from animal studies. CORT produces a different profile of effects than YOH (e.g. suppression of learning) and may augment YOH’s effect on opioid reinforcement. Financial support: 2 NIH R01 DA015462 and Joe Young Sr./Helene Lycacki Funds (State of Michigan) support this research.

Substantial enantiomer-specific differences in the neurochemical and behavioral actions of the synthetic cathinone mephedrone

Aims: Determine whether mu-opioid seeking, stress-related biomarkers, and associative learning are altered by manipulation of noradrenergic and glucocorticoid neurotransmission in heroindependent individuals. Methods: Subjects are being evaluated under buprenorphinemaintained, inpatient conditions using a 3×3 within-subject, randomized crossover, placebo-controlled, double-blind design. In each test session, oral pretreatment doses of the alpha2-adrenergic antagonist yohimbine (YOH 0, 27, 54mg) and glucocorticoid agonist hydrocortisone (CORT 0, 20, 40mg) are administered before a hydromorphone (HYD 1.5mg unit) vs. money ($2 unit) choice, progressive ratio task. Periodic measures include stress biomarkers (blood pressure, saliva cortisol and alpha-amylase), negative mood state, and hippocampal dependent (visual associative) learning measures. Results: In interim analyses (n=6 completers of 15 planned), YOH dose dependently increases HYD breakpoint (lin. F[1,5] = 6.37, p= .053), especially during CORT 40mg (lin. YOH×quadr. CORT F[1,5] = 10.77, p< .03). YOH dose dependently increases systolic and diastolic BP (lin. Fs[1,5] = 41.26 and 31.50, ps < .005); POMS Anxiety (lin. F[2,8]) = 2.71, p= .15; and associative learning rate (lin. F[1,5] = 6.11, p< .06), more so during placebo CORT (lin. YOH×quadratic CORT F[1,5] = 9.31, p< .03). YOH 27mg but not 54mg, relative to placebo, tends to increase cortisol (quadr. F[1,5] = 5.00, p<.08) but not alpha-amylase. CORT dose dependently increases cortisol (lin. F[1,5] = 32.20, p< .002) and decreases learning rate (lin. F[1,5] = 10.42,p< .03), but is not alteringother response measures. Conclusions: YOH-potentiated opioid seeking, blood pressure, and anxiety responses are consistent with Greenwald et al. (2013); emerging effects of YOH on cortisol and learning measures further validate this paradigm and extend findings from animal studies. CORT produces a different profile of effects than YOH (e.g. suppression of learning) and may augment YOH’s effect on opioid reinforcement. Financial support: 2 NIH R01 DA015462 and Joe Young Sr./Helene Lycacki Funds (State of Michigan) support this research.

The effects of nicotine stimulus and response expectancies on male and female smokers' responses to nicotine-free electronic cigarettes

BackgroundElectronic cigarettes (e-cigarettes) have been reported to reduce tobacco craving and withdrawal; however, the mechanisms underlying these effects have not been elucidated. MethodsThis study examined the contributions of nicotine stimulus and response expectancies to responses to nicotine-free e-cigarettes in 21 e-cigarette naïve smokers (12 male). Participants completed two randomized experimental sessions in which they administered a nicotine-free e-cigarette. During one session they were informed that the e-cigarette contained nicotine and during the other session they were informed that the e-cigarette was nicotine-free. Participants completed subjective assessments before and immediately after sampling ten puffs from the e-cigarette and were then invited to earn additional puffs using a computerized progressive ratio task. Prior to their enrolment in the study, participants provided an estimate of the relative importance of the nicotine content of e-cigarettes for craving relief. ResultsInstructions that the e-cigarette contained nicotine were found to reduce both intention to smoke (p=0.017) and withdrawal-related (p=0.018) craving, regardless of a-priori reported beliefs regarding the relative importance of nicotine. Nicotine content instructions were also found to be associated with a shorter latency to self-administration (p=0.005); however, a Sex×Instructions×Response Expectancy interaction (p=0.008) revealed that this effect was specific to women who had strong a-priori nicotine content craving relief expectations. Neither nicotine content instructions nor response expectancies impacted the number of puffs self-administered. ConclusionsFindings suggest that nicotine content expectations contribute to smokers' responses to e-cigarettes, and that a-priori beliefs about nicotine effects may be especially important in women.

Mechanisms of impulsive choice: I. Individual differences in interval timing and reward processing.

Impulsive choice behavior incorporates the psychological mechanisms involved in the processing of the anticipated magnitude and delay until reward. The goal of the present experiment was to determine whether individual differences in such processes related to individual differences in impulsive choice behavior. Two groups of rats (Delay Group and Magnitude Group) were initially exposed to an impulsive choice task with choices between smaller-sooner (SS) and larger-later (LL) rewards. The Delay Group was subsequently exposed to a temporal discrimination task followed by a progressive interval task, whereas the Magnitude Group was exposed to a reward magnitude sensitivity task followed by a progressive ratio task. Intertask correlations revealed that the rats in the Delay Group that made more self-controlled (LL) choices also displayed lower standard deviations in the temporal bisection task and greater delay tolerance in the progressive interval task. Impulsive choice behavior in the Magnitude Group did not display any substantial correlations with the reward magnitude sensitivity and progressive ratio tasks. The results indicate the importance of core timing processes in impulsive choice behavior, and encourage further research examining the effects of changes in core timing processes on impulsive choice.

Individual differences in impulsive and risky choice: Effects of environmental rearing conditions

The present experiment investigated early-rearing environment modulation of individual differences in impulsive and risky choice. Rats were reared in an isolated condition (IC; n=12), in which they lived alone without novel stimuli, or an enriched condition (EC; n=11), in which they lived among conspecifics with novel stimuli. The impulsive choice task involved choices between smaller-sooner (SS) versus larger-later (LL) rewards. The risky choice task involved choices between certain-smaller (C-S) versus uncertain-larger (U-L) rewards. Following choice testing, incentive motivation to work for food was measured using a progressive ratio task and correlated with choice behavior. HPLC analyses were conducted to determine how monoamine concentrations within the prefrontal cortex (PFC) and nucleus accumbens (NAC) related to behavior in different tasks. IC rats were more impulsive than EC rats, but they did not differ in risky choice behavior. However, choice behavior across tasks was significantly correlated (i.e., the more impulsive rats were also riskier). There were no group differences in monoamine levels, but noradrenergic and serotonergic concentrations were significantly correlated with impulsive and risky choice. Furthermore, serotonin and norepinephrine concentrations in the NAC significantly correlated with incentive motivation and the timing of the reward delays within the choice tasks. These results suggest a role for domain general processes in impulsive and risky choice and indicate the importance of the NAC and/or PFC in timing, reward processing, and choice behavior.

Amotivation in Schizophrenia: Integrated Assessment With Behavioral, Clinical, and Imaging Measures

Motivational deficits play a central role in disability caused by schizophrenia and constitute a major unmet therapeutic need. Negative symptoms have previously been linked to hypofunction in ventral striatum (VS), a core component of brain motivation circuitry. However, it remains unclear to what extent this relationship holds for specific negative symptoms such as amotivation, and this question has not been addressed with integrated behavioral, clinical, and imaging measures. Here, 41 individuals with schizophrenia and 37 controls performed a brief, computerized progressive ratio task (PRT) that quantifies effort exerted in pursuit of monetary reward. Clinical amotivation was assessed using the recently validated Clinical Assessment Interview for Negative Symptoms (CAINS). VS function was probed during functional magnetic resonance imaging using a monetary guessing paradigm. We found that individuals with schizophrenia had diminished motivation as measured by the PRT, which significantly and selectively related to clinical amotivation as measured by the CAINS. Critically, lower PRT motivation in schizophrenia was also dimensionally related to VS hypofunction. Our results demonstrate robust dimensional associations between behavioral amotivation, clinical amotivation, and VS hypofunction in schizophrenia. Integrating behavioral measures such as the PRT will facilitate translational efforts to identify biomarkers of amotivation and to assess response to novel therapeutic interventions.

(176) Behavioral response to monetary reward predicts lower pain sensitivity

Avoidance-oriented behaviors and cognitions, such as pain catastrophizing, are associated with pain sensitivity in both healthy and clinical populations, and promote vulnerability to chronic pain. Less is known about the extent to which approach-oriented behavior, the opponent process of avoidance, influences adaptation to chronic pain. The purpose of this study was to provide a preliminary evaluation of the association of performance on a classic behavioral approach task—the progressive ratio task—and pain sensitivity in response to quantitative sensory testing (QST). This study was a proof-of-concept pilot conducted in a subsample (N = 30) of a larger study that evaluated sleep and pain in older adults. During a 10 minute session, participants completed a progressive ratio task in which the number of button presses required to earn a 25 cent reinforcer systematically increased with each reinforcer earned. The primary outcome was total rewards (i.e., quarters) earned (M = 19.3, SD = 4.9), which is a behavioral measure of approach motivation. Participants subsequently underwent quantitative sensory testing (QST) of thermal and pressure threshold, and cold pain tolerance. Hierarchical regression results indicated that higher reward total was significantly associated with higher thermal threshold (p < .05), but not other QST measures. Reward total was significantly negatively correlated with pain catastrophizing (r = -.40; p < .05), but not depressive symptoms (r = -.22, p = .25). When catastrophizing was entered as a covariate, the effect of reward total on thermal threshold fell beyond the significance threshold (p = .12), but the magnitude of the effect was only minimally reduced. Thus, approach behavior appears to act in opposition to catastrophizing in predicting pain response, providing preliminary support for an approach-avoidance opponent process model of adaptation to chronic pain, which may have implications for chronic pain coping theory. Supported by NIH/NIAMS R01AR05487.

Exercise reinforcement, stress, and β-endorphins: An initial examination of exercise in anabolic–androgenic steroid dependence

BackgroundAnabolic–androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. MethodSixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity×frequency of exercise, age, and education abstained from exercise for 24h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image. ResultsBetween group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence. ConclusionThe HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence.

Fasting for 24 Hours Heightens Reward from Food and Food-Related Cues

IntroductionWe examined the impact of a 24 hour complete fast (vs. fed state) on two measures of food reward: 1) ‘wanting’, as measured by response to food images and by the relative-reinforcing value of food (RRV), and 2) ‘liking’, as measured by response to food images and the hedonic evaluation of foods consumed.MethodsUtilizing a randomized crossover design, 15 subjects (9 male; 6 female) aged 28.6±4.5 yrs with body mass index 25.3±1.4 kg/m2 were randomized and counterbalanced to normal feeding (FED) and 24-hour fast (FASTED) conditions. Trait characteristics were measured with the Three Factor Eating Questionnaire. Two computer tasks measured food reward: 1) RRV progressive ratio task, 2) explicit ‘liking’ and ‘wanting’ (Leeds Food Preference Questionnaire, LFPQ). Also measured were ad libitum energy intake (EI; buffet) and food ‘liking’ (visual analogue scale) of personalized stimuli.ResultsThere were no significant anthropometric changes between conditions. Appetite scores, hedonic ratings of ‘liking’, and ad libitum EI all significantly increased under the FASTED condition (p<0.05). Under the FASTED condition there were significant increases in the RRV of snack foods; similarly, explicit ‘wanting’ and ‘liking’ significantly increased for all food categories. ‘Liking’ of sweet foods remained high across-meals under FASTED, but savory foods decreased in hedonic saliency.ConclusionRelative to a fed state, we observed an increase in hedonic ratings of food, the rewarding value of food, and food intake after a 24 hr fast. Alliesthesia to food and food cues is suggested by heightened hedonic ratings under the FASTED condition relative to FED.

Reduced expression of nogo-a leads to motivational deficits in rats.

Nogo-A is an important neurite growth-regulatory protein in the adult and developing nervous system. Mice lacking Nogo-A, or rats with neuronal Nogo-A deficiency, exhibit behavioral abnormalities such as impaired short-term memory, decreased pre-pulse inhibition, and behavioral inflexibility. In the current study, we extended the behavioral profile of the Nogo-A deficient rat line with respect to reward sensitivity and motivation, and determined the concentrations of the monoamines dopamine and serotonin in the prefrontal cortex (PFC), dorsal striatum (dSTR), and nucleus accumbens (NAcc). Using a limited access consumption task, we found similar intake of a sweet condensed milk solution following ad libitum or restricted feeding in wild-type and Nogo-A deficient rats, indicating normal reward sensitivity and translation of hunger into feeding behavior. When tested for motivation in a spontaneous progressive ratio task, Nogo-A deficient rats exhibited lower break points and tended to have lower “highest completed ratios.” Further, under extinction conditions responding ceased substantially earlier in these rats. Finally, in the PFC we found increased tissue levels of serotonin, while dopamine was unaltered. Dopamine and serotonin levels were also unaltered in the dSTR and the NAcc. In summary, these results suggest a role for Nogo-A regulated processes in motivated behavior and related neurochemistry. The behavioral pattern observed resembles aspects of the negative symptomatology of schizophrenia.

The effect of snus on alcohol-related cigarette administration in dependent and non-dependent smokers

IntroductionAlcohol has been found to increase tobacco smoking in both dependent daily smokers (DDS) and nondependent nondaily smokers (NNS), yet little attention has been directed toward examining how different treatments/products modify drinking-related smoking behavior. MethodsThis study examined the acute effects of snus (4mg of nicotine) on alcohol-related smoking responses in 18 DDS and 17 NNS. During each double-blind session, participants were randomly assigned to receive one of the following combinations: alcohol and snus, alcohol and placebo snus, placebo alcohol and snus, or placebo alcohol and placebo snus. Participants consumed their assigned beverage before absorbing their session's product, and after 30min participants could self-administer puffs of their preferred brand of cigarette over a 60-minute period using a progressive ratio task. ResultsAlcohol significantly increased tobacco craving (p<.001) and tended to decrease latency to start smoking (p=.021) but only among NNS. In contrast, snus tended to decrease the number of puffs earned and how hard DDS worked for puffs in both beverage conditions (ps≤.019) but it did not alter the smoking behavior of NNS. Craving was not significantly impacted by snus in either type of smoker. DiscussionThese findings raise the possibility that different processes mediate alcohol and cigarette co-use in NNS and DDS and suggest that snus may be effective in reducing alcohol-related cigarette use in DDS specifically.

Poor nutrition during pregnancy and lactation negatively affects neurodevelopment of the offspring: evidence from a translational primate model

Studies of the effects of prenatal nutrition on neurodevelopment in humans are complicated because poor nutrition occurs in the context of psychosocial stressors and other risk factors associated with poor developmental outcomes. Under controlled experimental conditions, we tested an effect of prenatal nutrition on neurodevelopmental outcomes in the nonhuman primate. Juvenile offspring of 19 female baboons, whose diets were either restricted [maternal nutrition restriction (MNR)] or who were fed ad libitum (control), were administered the progressive ratio task from the Cambridge Neuropsychological Test Automated Battery. Activity, persistence, attention, and emotional arousal were coded from videotapes. These established, reliable methods were consistent with those used to assess individual differences in the behaviors of school-age children. MNR offspring (3 female and 4 male offspring) had significantly fewer responses and received fewer reinforcements on the progressive ratio task than did control offspring (8 female and 4 male offspring). MNR offspring showed a more variable activity level and less emotional arousal than did control offspring. Female MNR offspring showed more variable and lower levels of persistence and attention than did female control offspring. Thus, under controlled experimental conditions, data support a main effect of prenatal nutrition on highly translatable neurodevelopmental outcomes. Nutritional interventions during pregnancy have been successfully used to target neurodevelopmental problems, such as increasing folic acid intake during pregnancy to decrease the incidence of neural tube defects. Results from the current study can be used to support the testing of nutritional preventive interventions for the most-common childhood behavior problems.

The effects of nicotine content information on subjective and behavioural responses to nicotine-containing and denicotinized cigarettes

The effects of nicotine content information on subjective and behavioural responses to nicotine-containing and denicotinized cigarettes were examined in 30 dependent and 30 nondependent 12-h abstinent smokers. Using the four conditions of a balanced placebo design, participants were given either nicotine-containing cigarettes or denicotinized cigarettes during two laboratory sessions but were told that they received nicotine-containing cigarettes in one session and nicotine-free cigarettes in the other. During each session, participants completed subjective assessments before and after sampling three puffs from the assigned cigarette and were then invited to earn additional cigarette puffs using a computerized progressive ratio task. Regardless of the actual nicotine content, participants self-administered more cigarette puffs when they were told the cigarettes contained nicotine than when told the cigarettes were nicotine-free and tended to show a decrease in craving associated with the intention to smoke after cigarette sampling when told the cigarettes were nicotine-free relative to when they were told the cigarettes contained nicotine. However, regardless of nicotine instructions, participants given nicotine-containing cigarettes showed greater postsampling increases in subjective ratings of 'satisfied' and 'stimulated' than did those given denicotinized cigarettes. The findings suggest that nicotine dose expectancy can affect both subjective and behavioural indices of smoking reinforcement but that the satisfying and stimulating aspects of smoking are related to actual nicotine administration.

Genetic Reconstruction of Dopamine D1 Receptor Signaling in the Nucleus Accumbens Facilitates Natural and Drug Reward Responses

The dopamine D1 receptor (D1R) facilitates reward acquisition and its alteration leads to profound learning deficits. However, its minimal functional circuit requirement is unknown. Using conditional reconstruction of functional D1R signaling in D1R knock-out mice, we define distinct requirements of D1R in subregions of the nucleus accumbens (NAc) for specific dimensions of reward. We demonstrate that D1R expression in the core region of the NAc (NAc(Core)), but not the shell (NAc(Shell)), enhances selectively a unique form of pavlovian conditioned approach and mediates D1R-dependent cocaine sensitization. However, D1R expression in either the NAc(Core) or the NAc(Shell) improves instrumental responding for reward. In contrast, neither NAc(Core) nor NAc(Shell) D1R is sufficient to promote motivation to work for reward in a progressive ratio task or for motor learning. These results highlight dissociated circuit requirements of D1R for dopamine-dependent behaviors.

The Effects of Alcohol on Responses to Nicotine‐Containing and Denicotinized Cigarettes in Dependent and Nondaily Smokers

Alcohol consumption has been linked to increased tobacco use and craving in both dependent and nondaily smokers, yet the extent to which these relationships depend on interactions involving nicotine remains unclear. This study examined the acute effects of alcohol on the subjective and behavioral responses to nicotine-containing tobacco and denicotinized tobacco in 17 (10 male) dependent daily smokers (DDS) and 23 (11 male) nondependent nondaily smokers (NNS). During 4 randomized double-blind sessions, participants assessed the effects of nicotine-containing tobacco or denicotinized tobacco following the administration of a moderately intoxicating dose of alcohol (mean blood alcohol concentration = 0.076 g/dl) or a placebo beverage. They could then self-administer additional puffs of the same type of cigarette sampled over a 60-minute period using a progressive ratio task. In NNS, alcohol significantly increased the self-administration of both nicotine-containing and denicotinized cigarettes, and no differences in self-administration were observed between the 2 types of tobacco within either beverage condition. In contrast, in DDS, alcohol was associated with decreased denicotinized tobacco self-administration relative to the placebo beverage condition as well as with increased self-administration of nicotine-containing tobacco relative to denicotinized tobacco. DDS also exhibited relatively elevated craving following the administration of a nicotine-containing cigarette in the alcohol beverage condition. Findings suggest that nicotine may be critical to the drinking-smoking relationship in DDS, but that nonnicotine smoking factors may be more important in NNS.