Prenatal ethanol exposure impairs sensory processing and habituation to visual stimuli, effects normalized by enrichment of postnatal environmental.

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.

Moderate prenatal ethanol exposure leads to attention deficits in both male and female rats.

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.

Cocaine self-administration abolishes endocannabinoid-mediated long-term depression of glutamatergic synapses in the ventral tegmental area.

Drugs of abuse, including cocaine, alter the mechanisms underpinning synaptic plasticity, including long-term potentiation of glutamatergic synapses in the mesolimbic system. These effects are thought to underlie addictive behaviors. In the ventral tegmental area (VTA), glutamatergic synapses also exhibit long-term depression (LTD), a type of plasticity that weakens synaptic strength. This form of synaptic plasticity is induced by low-frequency stimulation and mediated by endocannabinoid (eCB) signaling, which also modulates addictive behaviors. However, it remains unknown whether eCB-LTD in the VTA could be altered by cocaine use. Therefore, the goal of the present study was to examine the impact of cocaine self-administration on eCB-LTD of glutamatergic synapses onto VTA dopaminergic (DA) neurons. To that end, male rats underwent cocaine (0.75 mg/kg/infusion) or saline self-administration under the fixed ratio 1 schedule for 6-9 days. One day after the last self-administration session, the magnitude of eCB-LTD was examined using ex vivo whole-cell recordings of putative VTA DA neurons from naïve rats and rats with saline or cocaine self-administration. The results revealed that cocaine self-administration abolished eCB-LTD. The cocaine-induced blockade of eCB-LTD in the VTA was mediated by an impaired function of presynaptic CB1 receptors. Collectively, these findings indicate that cocaine exposure blunts eCB-mediated synaptic plasticity in midbrain DA neurons. This effect could be one of the cellular mechanisms that mediate, at least in part, addictive behaviors.

Prenatal Ethanol Exposure and Postnatal Environmental Intervention Alter Dopaminergic Neuron and Microglia Morphology in the Ventral Tegmental Area During Adulthood.

BACKGROUND: Prenatal ethanol exposure (PE) impairs midbrain dopaminergic (DA) neuron function, which might contribute to various cognitive and behavioral deficits, including attention deficits and increased addiction risk, often observed in individuals with fetal alcohol spectrum disorders. Currently, the underlying mechanisms for PE-induced deficits are unclear. PE could lead to neuroinflammation by activating microglia, which play an important role in synaptic function. In the present study, we investigated PE effects on microglial activation and DA neuron density and morphology in the ventral tegmental area (VTA). Since postnatal environmental enrichment can reduce neuroinflammation and ameliorate several PE-induced behavioral deficits, we examined if a postnatal environmental intervention strategy using neonatal handling and postweaning complex housing could reverse PE effects on VTA DA neurons and microglia. METHODS: Pregnant rats received 0 or 6 g/kg/d ethanol by 2 intragastric intubations on gestation days 8 to 20. After birth, rats were reared in the standard laboratory or enriched condition. Male adult rats (8 to 12 weeks old) were used for immunocytochemistry. RESULTS: The results showed that PE decreased VTA DA neuron body size in standardly housed rats. Moreover, there was a significant decrease in numbers of VTA microglial branches and junctions in PE rats, suggesting morphological activation of microglia and possible neuroinflammation. The PE effects on microglia were normalized by postnatal environmental intervention, which also decreased the numbers of microglial branches and junctions in control animals, possibly via reduced stress. CONCLUSIONS: Our findings show an association between PE-induced morphological activation of microglia and impaired DA neuron morphology in the VTA. Importantly, postnatal environmental intervention rescues possible PE-induced microglial activation. These data support that environmental intervention can be effective in ameliorating cognitive and behavioral deficits associated with VTA DA neuron dysfunctions, such as attention deficits and increased addiction risk.

Prenatal ethanol exposure leads to persistent anxiety-like behavior during adulthood indicated by reduced horizontal and vertical exploratory behaviors.

Background: Fetal alcohol spectrum disorders (FASD) caused by prenatal ethanol exposure (PE) consist of many cognitive/behavioral deficits. Studies have reported that PE leads to impairments of learning and memory, attention, executive function, and anxiety. Open field (OF) is a common behavioral model which offers comprehensive ethological information. Here, we analyzed multiple parameters of OF to examine anxiety behavior and habituation after PE. Material and Methods: Pregnant Sprague Dawley rats were gavaged twice/day with 0 or 3 g/kg/treatment ethanol (15% w/v) during gestational day (GD) 8-20, mimicking second-trimester heavy PE in humans. The control and PE adult offspring were subjected to OF task in different ambient light levels with or without acute stress. Results: Prenatal ethanol exposure did not influence the overall locomotor activities or habituation in the OF. In lower ambient light, no PE effects could be detected. In higher ambient light, female PE rats showed less activities in the center zone, indicative of increased anxiety. Males show lower activities in the center zone only after acute stress. Rats spent <2% of the time in the center zone compared to >75% of the time in the corner zone where they engaged in frequent rearing activities (vertical exploration; exploratory rearing). Prenatal ethanol exposure led to lower rearing activities in the corner in both males and females. Acute stress masks the PE effects in males but not in females. Discussion: The results support that heavy PE leads to persistent anxiety-like behavior during adulthood in both sexes. This conclusion is supported by using multiple parameters of exploratory behavior in the OF, including the rearing activities in the corner to reach reliable quantification of anxiety-like behavior.

Adolescent chronic unpredictable stress leads to increased anxiety and attention deficit/hyperactivity-like symptoms in adulthood.

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.

Tonic Endocannabinoid Signaling Gates Synaptic Plasticity in Dorsal Raphe Nucleus Serotonin Neurons Through Peroxisome Proliferator-Activated Receptors.

Endocannabinoids (eCBs), which include 2-arachidonoylglycerol (2-AG) and anandamide (AEA) are lipid signaling molecules involved in the regulation of an array of behavioral and physiological functions. Released by postsynaptic neurons, eCBs mediate both phasic and tonic signaling at central synapses. While the roles of phasic eCB signaling in modulating synaptic functions and plasticity are well characterized, very little is known regarding the physiological roles and mechanisms regulating tonic eCB signaling at central synapses. In this study, we show that both 2-AG and AEA are constitutively released in the dorsal raphe nucleus (DRN), where they exert tonic control of glutamatergic synaptic transmission onto serotonin (5-HT) neurons. The magnitude of this tonic eCB signaling is tightly regulated by the overall activity of neuronal network. Thus, short term in vitro neuronal silencing or blockade of excitatory synaptic transmission abolishes tonic eCB signaling in the DRn. Importantly, in addition to controlling basal synaptic transmission, this study reveals that tonic 2-AG, but not AEA signaling, modulates synaptic plasticity. Indeed, short-term increase in tonic 2-AG signaling impairs spike-timing dependent potentiation (tLTP) of glutamate synapses. This tonic 2-AG-mediated homeostatic control of DRN glutamate synapses is not signaled by canonical cannabinoid receptors, but by intracellular peroxisome proliferator-activated receptor gamma (PPARγ). Further examination reveals that 2-AG mediated activation of PPARγ blocks tLTP by inhibiting nitric oxide (NO), soluble guanylate cyclase, and protein kinase G (NO/sGC/PKG) signaling pathway. Collectively, these results unravel novel mechanisms by which tonic 2-AG signaling integrates network activities and controls the synaptic plasticity in the brain.

Prenatal Ethanol Exposure Leads to Attention Deficits in Both Male and Female Rats.

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.

Prenatal ethanol exposure increases risk of psychostimulant addiction.

Prenatal ethanol exposure (PE) causes many cognitive and behavioral deficits including increased drug addiction risk, demonstrated by enhanced ethanol intake and behavioral phenotypes associated with addiction risk. Additionally, preclinical studies show that PE persistently changes the function of dopaminergic neurons in the ventral tegmental area, a major neural substrate for addiction, and alters these neurons' responses to psychostimulants. Accordingly, PE could also lead to increased risk of addiction to drugs of abuse, other than ethanol. In the present study, addiction risk was examined utilizing paradigms of amphetamine conditioned place preference (CPP) and intravenous self-administration. Ethanol was administered to pregnant dams via intragastric gavage (6 g/kg, during gestational days 8-20). Behavioral tests were conducted in adult male offspring. Amphetamine at a low dose (0.3 mg/kg, i.p.) induced CPP in PE but not control rats, whereas at a higher dose (0.6 mg/kg, i.p.) both groups acquired CPP. There was no group difference in amphetamine-induced CPP reinstatement. Furthermore, PE rats self-administered more amphetamine at a low dose (0.02 mg/kg/infusion) than controls, while no group differences were observed at a higher dose (0.1 mg/kg/infusion). Rats with PE also exhibited greater reactivity to contextual drug cues after extended abstinence and amphetamine-induced reinstatement of drug seeking. These results support that PE persistently leads to increased psychostimulant addiction risk later in life, manifested in many elements of addictive behavior following limited psychostimulant exposure. The observations provide insights into prevention strategies for drug addiction in individuals with fetal alcohol spectrum disorders.

Decreased environmental complexity during development impairs habituation of reinforcer effectiveness of sensory stimuli.

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.

Environmental enrichment reverses increased addiction risk caused by prenatal ethanol exposure.

Prenatal ethanol exposure (PE) leads to multiple cognitive and behavioral deficits including increased drug addiction risk. Previous studies have shown that rearing environment plays a significant role in impacting addiction risk. In the present study, we investigated if environmental enrichment during development could be effective in lowering the PE-induced increase in addiction risk. To simulate heavy drinking during pregnancy in humans, pregnant Sprague-Dawley rats received ethanol (6 g/kg/day) or vehicle through intragastric gavage on gestation days 8-20. After weaning, the offspring were reared in either an enriched environment (EE) including neonatal handling and complex housing or an impoverished environment (IE) consisting of barren, single housing. Adult male offspring were then tested for locomotion, performance on the elevated plus maze, and amphetamine self-administration under a progressive ratio reinforcement schedule. Overall, EE rats, compared to IE rats, showed reduced locomotor activity in a novel environment and lower levels of anxiety, irrespective of prenatal treatments. Prenatal ethanol exposure increased amphetamine self-administration at both doses tested (0.02 and 0.05 mg/kg/infusion) and in each case EE, relative to IE, reversed this effect. These findings suggest that postnatal environmental complexity plays a determining role in addiction risk after PE.

Nucleus accumbens lesions decrease sensitivity to rapid changes in the delay to reinforcement.

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.

Prenatal alcohol exposure causes attention deficits in male rats.

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.

Effects of morphine and naltrexone on impulsive decision making in rats.

RATIONALE: It has been reported that human opiate addicts discount delayed rewards more than non-addicts, indicating that they are more impulsive. However, it is not clear whether this difference reflects pre-existing traits, or the effects of exposure to the opiates. OBJECTIVES: This study was designed to investigate the effects of an opioid agonist and antagonist on delay discounting in rats. The study had three objectives: to determine (1) the acute effects of the opioid agonist morphine (MOR) on delay discounting, (2) the acute effects of the opioid antagonist naltrexone (NAL) on delay discounting, and (3) whether NAL reverses the effects of MOR on delay discounting. METHODS: An adjusting amount procedure (AdjAmt) was used to determine how much animals discounted the value of delayed rewards. Acute doses of MOR (0.3, 1.0, and 1.8 mg/kg SC), NAL (0.01, 0.1, 1.0, and 10 mg/kg SC) and NAL (0.1 mg/kg SC) prior to MOR (1.8 mg/kg SC) were tested in 15 rats. RESULTS: MOR dose dependently increased the rate of delay discounting (i.e., made the animals more impulsive). NAL alone had no effect on the value of delayed rewards, but NAL blocked the effects of MOR. CONCLUSIONS: These results suggested that the direct effects of MOR may contribute to the high level of impulsive behavior seen among opiate users.

Nicotine and methamphetamine disrupt habituation of sensory reinforcer effectiveness in male rats.

The reinforcing effectiveness of a sensory stimulus such as light-onset rapidly habituates (Lloyd, Gancarz, Ashrafioun, Kausch, & Richards, 2012). According to memory-based theories, habituation occurs if a memory exists for perceived stimulation, and dishabituation occurs if a memory does not exist and the stimulation is "unexpected." According to Redgrave and Gurney (2006), unexpected response-contingent sensory stimuli increase phasic firing of dopamine neurons, providing a sensory error signal that reflects the difference between perceived and expected stimuli. Together, memory-based theories of habituation and the sensory error signal hypothesis predict a disruption (slowing) of habituation rate by novel response-contingent sensory stimulation or by artificial increases in dopamine neurotransmission by stimulant drugs. To test these predictions, we examined the effects of stimulant drugs on both the operant level of responding (snout-poking) and operant responding for a sensory reinforcer (light-onset) presented according to a fixed ratio 1 schedule. Robust within-session decreases in responding indicating habituation were observed. The effects of stimulant drugs (saline, n = 10; nicotine, 0.40 mg/kg, n = 10; and methamphetamine, 0.75 mg/kg, n = 9) on habituation in rats were determined. Nicotine was found to decrease habituation rate and did not affect response rate, while methamphetamine decreased habituation rate and increased response rate. In addition, introduction of a novel visual stimulus reinforcer decreased habituation rate and increased responding. These findings show that habituation of reinforcer effectiveness modulates operant responding for sensory reinforcers, and that stimulant drugs may disrupt normally occurring habituation of reinforcer effectiveness by increasing dopamine neurotransmission.

Cerebral Developmental Abnormalities in a Mouse with Systemic Pyruvate Dehydrogenase Deficiency.

UNLABELLED: Pyruvate dehydrogenase (PDH) complex (PDC) deficiency is an inborn error of pyruvate metabolism causing a variety of neurologic manifestations. Systematic analyses of development of affected brain structures and the cellular processes responsible for their impairment have not been performed due to the lack of an animal model for PDC deficiency. METHODS: In the present study we investigated a murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene encoding the α subunit of PDH to study its role on brain development and behavioral studies. RESULTS: Male embryos died prenatally but heterozygous females were born. PDC activity was reduced in the brain and other tissues in female progeny compared to age-matched control females. Immunohistochemical analysis of several brain regions showed that approximately 40% of cells were PDH(-). The oxidation of glucose to CO2 and incorporation of glucose-carbon into fatty acids were reduced in brain slices from 15 day-old PDC-deficient females. Histological analyses showed alterations in several structures in white and gray matters in 35 day-old PDC-deficient females. Reduction in total cell number and reduced dendritic arbors in Purkinje neurons were observed in PDC-deficient females. Furthermore, cell proliferation, migration and differentiation into neurons by newly generated cells were reduced in the affected females during pre- and postnatal periods. PDC-deficient mice had normal locomotor activity in a novel environment but displayed decreased startle responses to loud noises and there was evidence of abnormal pre-pulse inhibition of the startle reflex. CONCLUSIONS: The results show that a reduction in glucose metabolism resulting in deficit in energy production and fatty acid biosynthesis impairs cellular differentiation and brain development in PDC-deficient mice.

Effects of reinforcer magnitude on an animal model of impulsive behavior.

The effects of altering sucrose solution concentration on discounting of delayed rewards in rats were examined. Five different delays were used (0, 1, 2, 4, and 8s) and three different sucrose solution concentrations (3, 10, and 30%). It was hypothesized that high value sucrose solution concentrations would be discounted less than low value sucrose solution concentrations. The results indicated that the rats discounted the 30% sucrose solution concentration at a higher rate than the 3 or 10% sucrose solution concentration, a finding that apparently contradicted the hypothesis that higher value sucrose solution concentrations would be discounted less than lower value sucrose solution concentrations. However, a follow up experiment indicated that the 3 and 10% sucrose solution concentrations were preferred over the 30% concentration. Thus the results of Experiment 1 can be interpreted as supporting the hypothesis that high valued sucrose solution concentrations are discounted less than lower valued sucrose solution concentrations.