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BACKGROUND: Individuals with fetal alcohol spectrum disorders (FASD) often show processing deficits in all sensory modalities. Using an operant light reinforcement model, we tested whether prenatal ethanol exposure (PE) alters operant responding to elicit a contingent sensory stimulus-light onset (turning on the light) and habituation to this behavior in rats. We also explored whether postnatal environmental enrichment could ameliorate PE-induced deficits. METHODS: Pregnant Sprague Dawley rats were gavaged twice/day with 0 or 3 g/kg/treatment ethanol (15% w/v) during gestational days 8-20, mimicking second-trimester heavy PE in humans. The offspring were reared in a standard housing condition or an enriched condition. Adult male and female offspring underwent an operant light reinforcement experiment with either a short-access or a long-access procedure. A dishabituation test was also conducted to characterize the habituation process. RESULTS: In the short-access procedure, PE led to increased operant responding to the contingent light onset in both sexes reared in the standard housing condition. Such an effect was not observed in rats reared in enriched conditions due to an overall decrease in responding. Moreover, rats reared in enriched conditions showed greater short-term habituation. In the long access procedure, PE rats showed increased responding and impaired long-term habituation. The long-access procedure facilitated both short-term and long-term habituation in control and PE rats. CONCLUSION: Prenatal ethanol exposure increases responding to contingent light onset and impairs the long-term habituation process. The PE-induced deficits were ameliorated by rearing in the enriched environment and increasing the duration and frequency of exposure to light onset. The PE-induced effects are like increased sensation-seeking, a subtype of sensory-processing deficit that is often observed in individuals with FASD. Our findings could inform a suitable animal model for investigating the underlying mechanisms and possible intervention strategies for sensory deficits in FASD.
Assuntos
Transtornos do Espectro Alcoólico Fetal , Animais , Etanol/toxicidade , Feminino , Habituação Psicofisiológica , Humanos , Masculino , Percepção , Gravidez , Ratos , Ratos Sprague-Dawley , SensaçãoRESUMO
BACKGROUND: Attention deficits caused by prenatal ethanol (EtOH) exposure (PE) are a prevalent condition in fetal alcohol spectrum disorders (FASDs). Importantly, the deficits are observed in individuals with FASD who have normal IQs and show no dysmorphic facial features caused by heavy PE. These observations suggest that even moderate PE could lead to attention deficits. This possibility was investigated in the present study using a rat model. METHODS: Pregnant Sprague Dawley rats were administered EtOH (3 g/kg/day) or vehicle via intragastric gavage on gestational days 8 to 20. The blood EtOH concentration (BEC) in EtOH-treated rats was 87.7 ± 1.2 mg/dl (1 h after the gavage), similar to the BECs reported in other moderate PE studies in rodents. Moderate PE did not produce teratogenic effects on birthweight or litter size. The adult offspring underwent a 2-choice reaction time task. RESULTS: Moderate PE led to augmented action impulsivity in both sexes, indicated by more rapid response initiation and more premature responses. Deficits were more marked in males than in females. No greater lapses of attention, assessed by incorrect or relatively slow responses, were observed in rats of either sex with moderate PE. In addition, no deficits in learning or motor function were detected after moderate PE. Interestingly, rats with moderate PE completed more trials than controls. CONCLUSIONS: Our results confirm that moderate PE leads to attention deficits in both sexes, which is demonstrated by greater action impulsivity, but not more lapses of attention. This effect differs from that of heavy PE, as shown in our previous study, which is manifested as impaired action impulsivity and lapses of attention in both sexes.
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Atenção/fisiologia , Depressores do Sistema Nervoso Central , Etanol , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Animais , Feminino , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Masculino , Gravidez , Ratos , Tempo de Reação/fisiologiaRESUMO
Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host of maladaptive behavioral traits associated with a range of neuropsychiatric disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This maladaptive dysregulation of behavior is influenced by genetic and environmental factors. For example, environmental enrichment produces beneficial neurobehavioral effects in animal models of such disorders. The present study determined the effects of environmental enrichment on a range of measures related to behavioral regulation using a large cohort of male, outbred heterogeneous stock (HS) rats as subjects. Subjects were reared from late adolescence onwards either in pairs in standard housing with minimal enrichment (n = 200) or in groups of 16 in a highly enriched environment consisting of a large multi-level cage filled with toys, running wheels, and shelters (n = 64). Rats were subjected to a battery of tests, including: (i) locomotor response to novelty, (ii) light reinforcement, (iii) social reinforcement, (iv) reaction time, (v) a patch-depletion foraging test, (vi) Pavlovian conditioned approach, (vii) conditioned reinforcement, and (viii) cocaine conditioned cue preference. Results indicated that rats housed in the enriched environment were able to filter out irrelevant stimuli more effectively and thereby regulate their behavior more efficiently than standard-housing rats. The dramatic impact of environmental enrichment suggests that behavioral studies using standard housing conditions may not generalize to more complex environments that may be more ethologically relevant.
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Cocaína , Humanos , Ratos , Animais , Masculino , Cocaína/farmacologia , Isolamento Social , Comportamento Animal/fisiologia , Abrigo para AnimaisRESUMO
Choice behavior requires animals to evaluate both short- and long-term advantages and disadvantages of all potential alternatives. Impulsive choice is traditionally measured in laboratory tasks by utilizing delay discounting (DD), a paradigm that offers a choice between a smaller immediate reward, or a larger more delayed reward. This study tested a large sample of Heterogeneous Stock (HS) male (n = 896) and female (n = 898) rats, part of a larger genetic study, to investigate whether measures of reward maximization overlapped with traditional models of delay discounting via the patch depletion model using a Sequential Patch Depletion procedure. In this task, rats were offered a concurrent choice between two water "patches" and could elect to "stay" in the current patch or "leave" for an alternative patch. Staying in the current patch resulted in decreasing subsequent reward magnitudes, whereas the choice to leave a patch was followed by a delay and a resetting to the maximum reward magnitude. Based on the delay in a given session, different visit durations were necessary to obtain the maximum number of rewards. Visit duration may be analogous to an indifference point in traditional DD tasks. While differences in traditional DD measures (e.g., delay gradient) have been detected between males and females, these effects were small and inconsistent. However, when examining measures of reward maximization, females made fewer patch changes at all delays and spent more time in the patch before leaving for the alternative patch compared to males. This pattern of choice resulted in males having a higher rate of reinforcement than females. Consistent with this, there was some evidence that females deviated from the optimal more, leading to less reward. Measures of reward maximization were only weakly associated with traditional DD measures and may represent distinctive underlying processes. Taken together, females performance differed from males with regard to reward maximization that were not observed utilizing traditional measures of DD, suggesting that the patch depletion model was more sensitive to modest sex differences when compared to traditional DD measures in a large sample of HS rats.
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Choice behavior requires animals to evaluate both short- and long-term advantages and disadvantages of all potential alternatives. Impulsive choice is traditionally measured in laboratory tasks by utilizing delay discounting (DD), a paradigm that offers a choice between a smaller immediate reward, or a larger more delayed reward. This study tested a large sample of Heterogeneous Stock (HS) male (n = 896) and female (n = 898) rats, part of a larger genetic study, to investigate whether measures of reward maximization overlapped with traditional models of delay discounting via the patch depletion model using a Sequential Patch Depletion procedure. In this task, rats were offered a concurrent choice between two water "patches" and could elect to "stay" in the current patch or "leave" for an alternative patch. Staying in the current patch resulted in decreasing subsequent reward magnitudes, whereas the choice to leave a patch was followed by a delay and a resetting to the maximum reward magnitude. Based on the delay in a given session, different visit durations were necessary to obtain the maximum number of rewards. Visit duration may be analogous to an indifference point in traditional DD tasks. Males and females did not significantly differ on traditional measures of DD (e.g. delay gradient; AUC). When examining measures of patch utilization, females made fewer patch changes at all delays and spent more time in the patch before leaving for the alternative patch compared to males. Consistent with this, there was some evidence that females deviated from reward maximization more than males. However, when controlling for body weight, females had a higher normalized rate of reinforcement than males. Measures of reward maximization were only weakly associated with traditional DD measures and may represent distinctive underlying processes. Taken together, females performance differed from males with regard to reward maximization that were not observed utilizing traditional measures of DD, suggesting that the patch depletion model was more sensitive to modest sex differences when compared to traditional DD measures in a large sample of HS rats.
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Desvalorização pelo Atraso , Ratos , Feminino , Masculino , Animais , Recompensa , Comportamento Impulsivo , Reforço Psicológico , Caracteres Sexuais , Comportamento de EscolhaRESUMO
Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host of maladaptive behavioral traits associated with a range of neuropsychiatric disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This maladaptive dysregulation of behavior is influenced by genetic and environmental factors. For example, environmental enrichment produces beneficial neurobehavioral effects in animal models of such disorders. The present study determined the effects of environmental enrichment on a range of measures related to behavioral regulation using a large cohort of male, outbred heterogeneous stock (HS) rats as subjects to mimic the genetic variability found in the human population. Subjects were reared from late adolescence onwards either in pairs in standard housing with minimal enrichment (n=200) or in groups of 16 in a highly enriched environment consisting of a large multi-level cage filled with toys, running wheels, and shelters (n=64). Rats were subjected to a battery of tests, including: (i) locomotor response to novelty, (iI) light reinforcement, (iii) social reinforcement, (iv) reaction time, (v) a patch-depletion foraging test, (vi) Pavlovian conditioned approach, (vii) conditioned reinforcement, and (viii) cocaine conditioned cue preference. Results indicated that rats housed in the enriched environment were able to filter out irrelevant stimuli more effectively and thereby regulate their behavior more efficiently than standard-housing rats. The dramatic impact of environmental enrichment suggests that behavioral studies using standard housing conditions may not generalize to more complex environments that may be more ethologically relevant.
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Power analyses are often used to determine the number of animals required for a genome-wide association study (GWAS). These analyses are typically intended to estimate the sample size needed for at least 1 locus to exceed a genome-wide significance threshold. A related question that is less commonly considered is the number of significant loci that will be discovered with a given sample size. We used simulations based on a real data set that consisted of 3,173 male and female adult N/NIH heterogeneous stock rats to explore the relationship between sample size and the number of significant loci discovered. Our simulations examined the number of loci identified in subsamples of the full data set. The subsampling analysis was conducted for 4 traits with low (0.15 ± 0.03), medium (0.31 ± 0.03 and 0.36 ± 0.03), and high (0.46 ± 0.03) SNP-based heritabilities. For each trait, we subsampled the data 100 times at different sample sizes (500, 1,000, 1,500, 2,000, and 2,500). We observed an exponential increase in the number of significant loci with larger sample sizes. Our results are consistent with similar observations in human GWAS and imply that future rodent GWAS should use sample sizes that are significantly larger than those needed to obtain a single significant result.
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Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Masculino , Feminino , Humanos , Animais , Ratos , Estudo de Associação Genômica Ampla/métodos , Tamanho da Amostra , Polimorfismo de Nucleotídeo Único , FenótipoRESUMO
BACKGROUND: Early-life adversities during development (e.g., child abuse and neglect) are linked to multiple behavioral and cognitive dysfunctions, such as attention deficit/hyperactivity disorder (ADHD) and anxiety disorders, which have high comorbidity. However, the impact of adversities during adolescence, a crucial period in early life for these disorders, is understudied. Using a chronic unpredictable stress (CUS) model in rats, we investigated whether adversities in adolescence could lead to increased anxiety and ADHD-like symptoms in adulthood. METHODS: Mid- to late-adolescent (5-7-week-old) male and female Sprague-Dawley rats underwent a mild CUS procedure for 2 weeks. Various stressors were applied in an unpredictable way. Rats of both sexes were then trained with a 2-choice reaction time (2-CRT) task during adulthood, which are designed to detect ADHD-like symptoms, including increased impulsivity and lapse of attention. In addition, an open field test was conducted to examine if CUS resulted in a persistent increase in anxiety-like behavior during adulthood. RESULTS: Both male and female rats with CUS exposure travelled shorter distances in the open field and spent less time in the center zone, indicating increased anxiety. In the 2-CRT task, rats of both sexes with CUS exposure showed increased impulsivity. Augmented lapses of attention were observed in female but not male rats. CONCLUSION: Chronic unpredictable stress during adolescence increases anxiety and leads to ADHD-like symptoms in both male and female rats in adulthood. The deficits are more severe in females than in males. These observations support that adversities during adolescence persistently increase anxiety, which is comorbid with attention deficits.
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Transtorno do Deficit de Atenção com Hiperatividade , Animais , Feminino , Masculino , Ratos , Ansiedade/psicologia , Transtornos de Ansiedade , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Ratos Sprague-DawleyRESUMO
BACKGROUND: Prenatal ethanol exposure (PE) causes multiple behavioral and cognitive deficits, collectively referred to as fetal alcohol spectrum disorders (FASD). Studies show that 49-94% of FASD children exhibit attention deficits, even when they have normal IQs or lack severe facial deformities, suggesting that attention deficits could be caused by even moderate prenatal exposure to alcohol, of which the underlying neural mechanisms are still unclear. A valid rodent model could help elucidate this phenomenon. MATERIALS AND METHODS: A second-trimester equivalent binge drinking PE model was utilized. Pregnant Sprague Dawley rats were administered with 15% (w/v) ethanol (6 g/kg/day, via gastric gavage) during gestational days 8-20, and their offspring were the subjects in the present study. A modified 2-choice reaction time (2-CRT) task was used to illustrate possible attention deficits, including increased action impulsivity and lapses of attention. Enhanced impulsivity was reflected by more premature responses while increased lapses of attention were manifested as more incorrect responses and/or greater variability of reaction time, demonstrated by more skewed distributions of reaction time. Ten-week-old male and female rats were tested for three sessions following 16-19 days of training. RESULTS: Our PE paradigm caused no major teratogenic effects. PE led to increased impulsivity exhibited as greater premature responses and augmented lapses of attention shown by greater skewnesses of reaction time distributions, relative to controls. The deficits were observed in both PE male and female rats. Interestingly, in males, the attention deficits were detected only when the 2-CRT task was relatively difficult whereas in females they were detected even when the task was at a less demanding level. CONCLUSION: We show that the binge drinking pattern of PE led to attention deficits in both sexes of rats even though no major teratogenic effects were observed. Therefore, this rodent model can be used to study neural mechanisms underlying attention deficits caused by PE and to explore effective intervention approaches for FASD.
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BACKGROUND: Multiple factors contribute to the etiology of addiction, including genetics, sex, and a number of addiction-related behavioral traits. One behavioral trait where individuals assign incentive salience to food stimuli ("sign-trackers", ST) are more impulsive compared to those that do not ("goal-trackers", GT), as well as more sensitive to drugs and drug stimuli. Furthermore, this GT/ST phenotype predicts differences in other behavioral measures. Recent studies have implicated the gut microbiota as a key regulator of brain and behavior, and have shown that many microbiota-associated changes occur in a sex-dependent manner. However, few studies have examined how the microbiome might influence addiction-related behaviors. To this end, we sought to determine if gut microbiome composition was correlated with addiction-related behaviors determined by the GT/ST phenotype. METHODS: Outbred male (N=101) and female (N=101) heterogeneous stock rats underwent a series of behavioral tests measuring impulsivity, attention, reward-learning, incentive salience, and locomotor response. Cecal microbiome composition was estimated using 16S rRNA gene amplicon sequencing. Behavior and microbiome were characterized and correlated with behavioral phenotypes. Robust sex differences were observed in both behavior and microbiome; further analyses were conducted within sex using the pre-established goal/sign-tracking (GT/ST) phenotype and partial least squares differential analysis (PLS-DA) clustered behavioral phenotype. RESULTS: Overall microbiome composition was not associated to the GT/ST phenotype. However, microbial alpha diversity was significantly decreased in female STs. On the other hand, a measure of impulsivity had many significant correlations to microbiome in both males and females. Several measures of impulsivity were correlated with the genus Barnesiella in females. Female STs had notable correlations between microbiome and attentional deficient. In both males and females, many measures were correlated with the bacterial families Ruminocococcaceae and Lachnospiraceae. CONCLUSIONS: These data demonstrate correlations between several addiction-related behaviors and the microbiome specific to sex.
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Transtornos Relacionados ao Uso de Cocaína/microbiologia , Cocaína/farmacologia , Condicionamento Operante/efeitos dos fármacos , Desvalorização pelo Atraso/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Reforço Psicológico , Animais , Animais não Endogâmicos , Bacteroidetes/classificação , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Ceco/microbiologia , Clostridiales/classificação , Clostridiales/genética , Clostridiales/isolamento & purificação , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Condicionamento Operante/fisiologia , Desvalorização pelo Atraso/fisiologia , Euryarchaeota/classificação , Euryarchaeota/genética , Euryarchaeota/isolamento & purificação , Feminino , Firmicutes/classificação , Firmicutes/genética , Firmicutes/isolamento & purificação , Microbioma Gastrointestinal/genética , Comportamento Impulsivo/fisiologia , Locomoção/fisiologia , Masculino , Fenótipo , Proteobactérias/classificação , Proteobactérias/genética , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S/genética , Ratos , Fatores SexuaisRESUMO
The stimulant, methylphenidate (MPH), is commonly used to treat attention deficit hyperactivity disorder (ADHD) and has been increasingly prescribed for school age children and adolescents. Concerns regarding its long-term effects on later substance use disorders (SUDs) have been raised. Previous animal studies have produced contradictory results regarding whether early exposure to MPH increases or protects against SUD in adulthood. The goal of our study was to determine if clinically relevant doses of MPH during adolescence alter cocaine responsiveness in adulthood in a rat model of ADHD, the spontaneous hypertensive rat (SHR). We pretreated SHRs with saline or MPH (2.5 mg/kg once or twice day) via oral gavage during their dark cycle from postnatal day 35 (p35) to p44. Adult rats (p80) were assessed in an eight-session cocaine-conditioned place preference test (CPP). Four doses of cocaine were administered via intraperitoneal injection (i.p.) during the conditioning sessions: 1, 5, 10 and 20 mg/kg. Once per day MPH treatment had a small sensitizing effect on baseline general locomotor activity in a novel environment at p80 as well as a limited suppressive effect on reward-specific locomotor activity as measured by the decreased preference to enter the cocaine-paired chamber. This treatment did not have any effect on the amount of time that rats chose to spend in the cocaine-paired chamber. Twice per day MPH treatment had no effect on locomotion or drug-preference. Our results suggest that MPH treatment of ADHD rats during adolescence does not alter preference for cocaine in adulthood.
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Previous research has shown that rats reared in simple/impoverished environments demonstrate greater repetitive responding for sensory reinforcers (e.g., light onset). Moreover, the brains of these rats are abnormally developed, compared to brains of rats reared in more complex/enriched environments. Repetitive behaviors are commonly observed in individuals with developmental disorders. Some of these repetitive behaviors could be maintained by the reinforcing effects of the sensory stimulation that they produce. Therefore, rearing rats in impoverished conditions may provide an animal model for certain repetitive behaviors associated with developmental disorders. We hypothesize that in rats reared in simple/impoverished environments, the normal habituation process to sensory reinforcers is impaired, resulting in high levels of repetitive behaviors. We tested the hypothesis using an operant sensory reinforcement paradigm in rats reared in simple/impoverished (IC), standard laboratory (SC), and complex/enrichened conditions (EC, treatments including postnatal handling and environmental enrichment). Results show that the within-session habituation of the reinforcer effectiveness of light onset was slower in the IC and SC rats than in the EC rats. A dishabituation challenge indicated that within-session decline of responses was due to habituation and not motor fatigue or sensory adaptation. In conclusion, rearing rats in simple/impoverished environments, and comparing them to rats reared in more complex/enriched environments, may constitute a useful approach for studying certain repetitive behaviors associated with developmental disorders.
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Deficiências do Desenvolvimento/etiologia , Meio Ambiente , Habituação Psicofisiológica/fisiologia , Reforço Psicológico , Comportamento Estereotipado/fisiologia , Visão Ocular/fisiologia , Fatores Etários , Análise de Variância , Animais , Área Sob a Curva , Condicionamento Operante/fisiologia , Deficiências do Desenvolvimento/psicologia , Modelos Animais de Doenças , Manobra Psicológica , Luz , Masculino , Ratos , Ratos Sprague-Dawley , Esquema de ReforçoRESUMO
BACKGROUND: Stimulant drugs such as nicotine (NIC) and methylphenidate (MPH) are hypothesized to increase the reinforcing value of sensory stimuli, thus increasing the effectiveness of such reinforcers as alternatives to sucrose reinforcers. METHODS: Inbred Fischer-344 rats (n = 30) were assigned to three groups: saline (SAL; n = 10), nicotine (NIC; n = 10), or methylphenidate (MPH; n = 10). Testing was done in three phases: sucrose only, (SUC), sucrose and drug (SUC/DRUG), and sucrose, drug, and social reinforcement (SUC/DRUG/SOC). During the SUC phase, rats were trained on a progressive ratio 5 (PR5) reinforcement schedule for sucrose (20% solution). In the SUC/DRUG phase, animals were treated with SAL, NIC (0.4 mg/kg, n = 10 SC), or MPH (2.0 mg/kg, n = 10 IP) 30 min prior to testing. In the SUC/DRUG/SOC phase, animals continued receiving drug treatment, and social reinforcement was introduced concurrently with the sucrose reinforcer. The progressive ratio for each reinforcer ran independently of the others. Reinforcing value was measured as break point (BP), the highest number of responses resulting in a reinforcer. RESULTS: SAL-treated animals showed no significant change in sucrose BP. MPH-treated animals showed decreased sucrose BP in the SUC/DRUG phase, with a further reduction in the SUC/DRUG/SOC phase. NIC-treated animals decreased sucrose BP only when a social alternative was offered. CONCLUSION: Both NIC and MPH reduce the sucrose BP in the presence of a social alternative. The decrease in sucrose responding, coupled with increased social responding, suggests that the social alternative acted as an effective alternative reinforcer to sucrose. From a translational perspective, these results suggest that stimulant drugs such as NIC and MPH may increase the effectiveness of treatments that use alternative social reinforcers to decrease eating.
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Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Condicionamento Operante/efeitos dos fármacos , Metilfenidato/farmacologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Reforço Social , Edulcorantes/farmacologia , Animais , Economia Comportamental , Masculino , Ratos , Ratos Endogâmicos F344 , Esquema de Reforço , Reforço Psicológico , Sacarose/farmacologiaRESUMO
In humans, prepulse inhibition (PPI) of startle is greater during attended prestimuli than it is during ignored prestimuli, whereas in rats, most work has focused on passive PPI, which does not require attention. In the work described in this article, researchers developed a paradigm to assess attentional modification of PPI in rats using motivationally salient prepulses. Water-deprived rats were either conditioned to attend to a conditioned stimulus (CS; 1-s, 7-dB increase in white noise) paired with water (CS(+) group), or they received uncorrelated presentations of white noise and water (CS0 group). After 10 conditioning sessions, startle probes (50 ms, 115 dB) were introduced, with the CS serving as a continuous prepulse. Three experiments examined PPI across a range of prepulse intensities (4-10 dB) and stimulus onset asynchronies (SOAs; 30-960 ms). PPI was consistently reduced in the CS(+) group, particularly with a 10-dB prepulse and a 60-ms SOA. Thus, PPI in rats differed between attended and ignored prestimuli, but the effect was reversed in the results of research with humans. A fourth study eliminated the group difference by reversing the CS-water contingency. Methodological and motivational hypotheses regarding the current findings are discussed.
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Atenção/fisiologia , Condicionamento Clássico/fisiologia , Inibição Psicológica , Motivação , Reflexo de Sobressalto/fisiologia , Reforço Psicológico , Estimulação Acústica/métodos , Análise de Variância , Animais , Comportamento Animal , Relação Dose-Resposta à Radiação , Masculino , Ratos , Ratos Sprague-Dawley , Tempo de ReaçãoRESUMO
The purpose of this study was to examine the effects of sleep deprivation on impulsive behavior. Patients with impulse control disorders often report sleep problems, and sleep deprivation even in healthy individuals impairs cognition, decision-making, and perhaps impulse control. To characterize the effects of sleep loss on specific forms of impulsive behavior, we tested the effects of overnight, monitored sleep deprivation on measures of impulsivity and cognition in healthy volunteers. Ten men and ten women completed two 24 h sessions in random order, in which they were either allowed to sleep normally or remained awake all night. At 8:30 am and 6:15 pm on the day after sleep or no sleep, participants were tested on the Balloon Analogue Risk Task (BART), the Experiential Discounting Task, the Adjusting Amount Delay and Probability Discounting Task, and the Stop Task. Participants also completed mood questionnaires and the Automated Neuropsychological Assessment Matrix (ANAM) throughout the course of the day. Sleep deprivation did not affect most of the measures of impulsive behavior. However, on the BART, sleep deprivation decreased risk taking in women, but not men. Sleep deprivation produced expected increases in subjective fatigue, and impaired performance on measures of attention and cognitive efficiency on the ANAM. The results indicate that sleep deprivation does not specifically increase impulsive behaviors but may differentially affect risk taking in men and women.
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Comportamento Impulsivo/psicologia , Privação do Sono/psicologia , Adolescente , Adulto , Feminino , Jogos Experimentais , Humanos , Comportamento Impulsivo/complicações , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valores de Referência , Medição de Risco , Privação do Sono/complicaçõesRESUMO
Both humans and non-humans discount the value of rewards that are delayed or uncertain, and individuals that discount delayed rewards at a relatively high rate are considered impulsive. To investigate the neural mechanisms that mediate delay discounting, the present study examined the effects of excitotoxic lesions of the nucleus accumbens (NAC) on discounting of reward value by delay and probability. Rats were trained on delay (n=24) or probability discounting (n=24) tasks. Following training, excitotoxic lesions of the NAC were made by intracranial injections of 0.5 microl 0.15 M quinolinic acid (n=12) or vehicle (n=12) aimed at the NAC (AP +1.6, ML +/-1.5, DV -7.1). NAC lesions did not alter performance in animals tested with a constant delay (4s) or probability (0.4) of reinforcement. However, when tested with between session changes in the delay (0, 1, 2, 4, and 8s) of reinforcement, the lesioned rats had flatter discount curves than the sham group, indicating that they were less sensitive to frequent changes in the delay to reward. In contrast, the NAC lesions did not affect discounting of probabilistic rewards. NAC lesions impaired the ability to adapt to frequent between session changes in the delay to reward but did not increase or decrease discounting when the delay was held constant across sessions. NAC lesions may disrupt the ability of the animals to predict the timing of delayed rewards when the delay to reward is changed frequently.
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Lesões Encefálicas/patologia , Núcleo Accumbens/fisiopatologia , Tempo de Reação/fisiologia , Reforço Psicológico , Animais , Comportamento Animal , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Lesões Encefálicas/induzido quimicamente , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Imuno-Histoquímica/métodos , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Núcleo Accumbens/lesões , Fosfopiruvato Hidratase/metabolismo , Probabilidade , Ácido Quinolínico/toxicidade , Ratos , Ratos Sprague-Dawley , Esquema de Reforço , Fatores de TempoRESUMO
Alcohol is widely believed to increase impulsive behavior. However, this has been difficult to demonstrate for impulsive choice using existing measures of delay discounting. We hypothesized a new real-time discounting task would be more sensitive to acute effects of alcohol. Measures included were a (a) question-based measure of delay discounting, the (b) Experiential Discounting Task (EDT), the (c) Balloon Analogue Risk Task (BART), the (d) Stop Task, and the (e) Go/No-Go Task. A three-session, double-blind, placebo-controlled, within-subjects design was used. Placebo, 0.4, or 0.8 g/kg alcohol doses were administered in a counterbalanced order over the three testing sessions. Twenty four (13 females) healthy social drinkers between the ages of 21 and 35 participated. Alcohol increased impulsive responding only on the EDT and the Stop Task. On the EDT, participants performed more impulsively after the 0.8 g/kg dose compared to placebo, whereas on the Stop Task, both the 0.4 and 0.8 g/kg doses increased impulsive responding. Alcohol had no significant effects on the other measures. The EDT was more sensitive to the acute effects of alcohol than previously used discounting tasks. Procedural differences between the EDT and question-based measures are discussed in the context of these divergent findings.
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Etanol/farmacologia , Análise e Desempenho de Tarefas , Adulto , Relação Dose-Resposta a Droga , Etanol/administração & dosagem , Feminino , Humanos , MasculinoRESUMO
There are reports that diazepam can increase, decrease, or have no effect on measures of impulsive behavior, which may be related, in part, to differences among the tasks used to measure impulsivity. This study examined the effects of a relatively high dose of diazepam (20 mg) on 5 measures of impulsive behavior in healthy adult men and women. Volunteers (N = 18) participated in a 2-session double-blind randomized design in which they received 20 mg diazepam or placebo. One hour after ingesting the capsule, participants completed mood questionnaires and several impulsivity tasks to measure subtypes of impulsive behavior, including behavioral inhibition, delay and probability discounting, and risk taking. Diazepam impaired behavioral inhibition but had no effect on measures of discounting or risk taking. These results are discussed in the context of other recent findings suggesting that different behavioral indices of impulsivity are dissociable and governed by separate underlying mechanisms.
Assuntos
Diazepam/farmacologia , Comportamento Impulsivo , Inibição Psicológica , Assunção de Riscos , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
RATIONALE: Disorders of behavioral regulation, including attention deficit hyperactivity disorder (ADHD) and drug addiction, are in part due to poor inhibitory control, attentional deficits, and hyper-responsivity to reward-associated cues. OBJECTIVES: To determine whether these traits are related, we tested genetically variable male and female heterogeneous stock rats in the choice reaction time (CRT) task and Pavlovian conditioned approach (PavCA). Sex differences in the response to methylphenidate during the CRT were also assessed. METHODS: In the CRT task, rats were required to withhold responding until one of two lights indicated whether responses into a left or right port would be reinforced with water. Reaction time on correct trials and premature responses were the operational definitions of attention and response inhibition, respectively. Rats were also pretreated with oral methylphenidate (0, 2, 4 mg/kg) during the CRT task to determine whether this drug would improve performance. Subsequently, during PavCA, presentation of an illuminated lever predicted the delivery of a food pellet into a food-cup. Lever-directed approach (sign-tracking) and food-cup approach (goal-tracking) were the primary measures, and rats were categorized as "sign-trackers" and "goal-trackers" using an index based on these measures. RESULTS: Sign-trackers made more premature responses than goal-trackers but showed no differences in reaction time. There were sex differences in both tasks, with females having higher sign-tracking, completing more CRT trials, and making more premature responses after methylphenidate administration. CONCLUSIONS: These results indicate that response inhibition is related to reward-cue responsivity, suggesting that these traits are influenced by common genetic factors.
Assuntos
Comportamento de Escolha/fisiologia , Condicionamento Clássico/fisiologia , Comportamento Alimentar/psicologia , Animais , Sinais (Psicologia) , Feminino , Alimentos , Inibição Psicológica , Masculino , Modelos Animais , Motivação , Ratos , Ratos Sprague-Dawley , Tempo de Reação , RecompensaRESUMO
Children with fetal alcohol spectrum disorder (FASD) are often diagnosed with attention-deficit/ hyperactivity disorder (ADHD). These children show increases in reaction time (RT) variability and false alarms on choice reaction time (CRT) tasks. In this study, adult rats prenatally exposed to ethanol were trained to perform a CRT task. An analysis of the distribution of RTs obtained from the CRT task found that rats with a history of prenatal ethanol exposure had more variable RT distributions, possibly because of lapses of attention. In addition, it was found that, similar to children with FASD, the ethanol-exposed rats had more false alarms. Thus, rats with prenatal ethanol exposure show attention deficits that are similar to those of children with FASD and ADHD.