No evidence tube entrapment distresses rodents in typical empathy tests.

In the first two experiments an empty tube open at one end was placed in different locations. Male hamsters, tested one at a time, tended to stay close to the tube or in it. During the first minute of the first 4 sessions of Experiment 3, the hamster was unrestrained. If it entered the tube, it was locked within the tube. If it did not enter the tube during the first min, it was placed in it, and the tube was locked. Fifteen min later, the tube was opened, and the hamster was unrestrained for a further 20 min. The tube remained open during Session 5. Hamsters spent more time near the tube than predicted by chance and continued to enter the tube although tube-occupancy duration did not differ from chance levels. In Experiment 4, male rats were tested in two groups: rats in one group had been previously trapped in a tube and rats in the other group allowed to freely explore the test space. For the first two min of each of four 20-min sessions, trapped-group subjects were permitted to move about the chamber unless they entered the tube. In that case, they were locked in for the remainder of the session. If, after two min, they did not enter the tube, they were locked in it for the remaining 18 min. Free rats were unrestricted in all sessions. In Session 5, when both groups were permitted to move freely in the chamber, trapped and free rats spent more time in and near the tube than predicted by chance. These data show tube restraint does not seem to distress either hamsters or rats.

Management of syncope in the Emergency Department: a European prospective cohort study (SEED).

BACKGROUND AND IMPORTANCE: In 2018, the European Society of Cardiology (ESC) produced syncope guidelines that for the first-time incorporated Emergency Department (ED) management. However, very little is known about the characteristics and management of this patient group across Europe. OBJECTIVES: To examine the prevalence, clinical presentation, assessment, investigation (ECG and laboratory testing), management and ESC and Canadian Syncope Risk Score (CSRS) categories of adult European ED patients presenting with transient loss of consciousness (TLOC, undifferentiated or suspected syncope). DESIGN: Prospective, multicentre, observational cohort study. SETTINGS AND PARTICIPANTS: Adults (≥18 years) presenting to European EDs with TLOC, either undifferentiated or thought to be of syncopal origin. MAIN RESULTS: Between 00:01 Monday, September 12th to 23:59 Sunday 25 September 2022, 952 patients presenting to 41 EDs in 14 European countries were enrolled from 98 301 ED presentations (n = 40 sites). Mean age (SD) was 60.7 (21.7) years and 487 participants were male (51.2%). In total, 379 (39.8%) were admitted to hospital and 573 (60.2%) were discharged. 271 (28.5%) were admitted to an observation unit first with 143 (52.8%) of these being admitted from this. 717 (75.3%) participants were high-risk according to ESC guidelines (and not suitable for discharge from ED) and 235 (24.7%) were low risk. Admission rate increased with increasing ESC high-risk factors; 1 ESC high-risk factor; n = 259 (27.2%, admission rate=34.7%), 2; 189 (19.9%; 38.6%), 3; 106 (11.1%, 54.7%, 4; 62 (6.5%, 60.4%), 5; 48 (5.0%, 67.9%, 6+; 53 (5.6%, 67.9%). Furthermore, 660 (69.3%), 250 (26.3%), 34 (3.5%) and 8 (0.8%) participants had a low, medium, high, and very high CSRS respectively with respective admission rates of 31.4%, 56.0%, 76.5% and 75.0%. Admission rates (19.3-88.9%), use of an observation/decision unit (0-100%), and percentage high-risk (64.8-88.9%) varies widely between countries. CONCLUSION: This European prospective cohort study reported a 1% prevalence of syncope in the ED. 4 in 10 patients are admitted to hospital although there is wide variation between country in syncope management. Three-quarters of patients have ESC high-risk characteristics with admission percentage rising with increasing ESC high-risk factors.

A test of the role of stimulus-response and stimulus-outcome associations in the effects of intermittent-access training.

Increased reinforcer motivation in rats has been repeatedly demonstrated following intermittent-access (IntA) training, where the reinforcer is only available for brief periods during a session, compared to continuous-access (ContA) training where the reinforcer is available throughout the session. The present study investigated whether different associations learned during training on the two procedures contributes to the effect. Two experiments tested the importance of the stimulus-response (S-R) and stimulus-outcome (S-O) associations between the IntA availability cues and the training response and reinforcer, respectively. In Exp. 1, separate groups of rats were trained to lever press for saccharin on the IntA or ContA procedures. Increased motivation for saccharin was observed in the IntA group on a later progressive ratio test where nosepoking was the operant (but not when lever pressing was the operant). The outcome of the nosepoke test suggests that a potential S-R association formed during IntA training was not critical for the effect. In Exp. 2, increased saccharin motivation (on nosepoke tests) after IntA training (with lever pressing) was observed regardless of the presence or absence of IntA availability cues, indicating that the S-O association formed during training is not critical for the effect either. Overall, these results suggest that the elemental associations learned on IntA procedures may not be what drives increased motivation observed after IntA training.

Cocaine and heroin interact differently with nondrug reinforcers in a choice situation.

The present study used a rat choice model to test how cocaine or heroin economically interacted with two different nondrug reinforcers along the substitute-to-complement continuum. In Experiment 1, the nondrug alternative was the negative reinforcer timeout-from-avoidance (TOA)-that is, rats could press a lever to obtain a period of safety from footshock. One group of rats chose between cocaine and TOA and another group chose between heroin and TOA. The relative prices of the reinforcers were manipulated across phases while controlling for potential income effects. When cocaine was the reinforcer, rats reacted to price changes by increasing their allocation of behavior to the more expensive option, thereby maintaining relatively proportional intake of cocaine and TOA reinforcers across prices, suggesting these reinforcers were complements here. In contrast, when heroin became relatively cheap, rats increased allocation of income to heroin and decreased allocation of income to TOA, suggesting that heroin substituted for safety. Additionally, rats were willing to accept more footshocks when heroin was easily available. In Experiment 2, the nondrug alternative was saccharin, a positive reinforcer. Heroin and saccharin were complements, but there was no consistent effect of price changes on the allocation of behavior between cocaine and saccharin. As a model of the processes that could be involved in human drug use, these results show that drug-taking behavior depends on the type of drug, the type of nondrug alternative available, and the prices of both. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Intermittent-access operant alcohol self-administration promotes binge-like drinking and drinking despite negative consequences in male and female heterogeneous stock rats.

The study of Alcohol Use Disorders (AUD) in preclinical models is hampered by difficulty in training rodents to voluntarily consume high levels of alcohol. The intermittency of alcohol access/exposure is well known to modulate alcohol consumption (e.g., alcohol deprivation effect, intermittent-access two-bottle-choice) and recently, intermittent access operant self-administration procedures have been used to produce more intense and binge-like self-administration of intravenous psychostimulant and opioid drugs. In the present study, we sought to systematically manipulate the intermittency of operant self-administered alcohol access to determine the feasibility of promoting more intensified, binge-like alcohol consumption. To this end, 24 male and 23 female NIH Heterogeneous Stock rats were trained to self-administer 10% w/v ethanol, before being split into three different-access groups. Short Access (ShA) rats continued receiving 30-min training sessions, Long Access (LgA) rats received 16-h sessions, and Intermittent Access (IntA) rats received 16-h sessions, wherein the hourly alcohol-access periods were shortened over sessions, down to 2 min. IntA rats demonstrated an increasingly binge-like pattern of alcohol drinking in response to restriction of alcohol access, while ShA and LgA rats maintained stable intake. All groups were tested on orthogonal measures of alcohol-seeking and quinine-punished alcohol drinking. The IntA rats displayed the most punishment-resistant drinking. In a separate experiment, we replicated our main finding, that intermittent access promotes a more binge-like pattern of alcohol self-administration using 8 male and 8 female Wistar rats. In conclusion, intermittent access to self-administered alcohol promotes more intensified self-administration. This approach may be useful in developing preclinical models of binge-like alcohol consumption in AUD.

Intermittent access cocaine self-administration produces context-specific escalation and increased motivation.

The intermittent-access (IntA) self-administration procedure has been reported to produce intensified addiction-like behavior compared to continuous-access (ContA) procedures. In a common variation of the IntA procedure, cocaine is available for 5 min at the beginning of each half hour of a 6-h session. In contrast, during ContA procedures, cocaine is available continuously throughout a session, typically lasting one or more hours. Previous studies comparing procedures have used between-subjects designs, where separate groups of rats self-administer cocaine on either IntA or ContA procedures. The present study used a within-subjects design where subjects self-administered cocaine on the IntA procedure in one context and self-administered cocaine on the continuous short-access (ShA) procedure in another context during separate sessions. Across sessions, rats escalated cocaine intake in the IntA, but not ShA, context. Following sessions eight and 11, rats were administered a progressive ratio test in each context to monitor the change in cocaine motivation. Rats obtained more cocaine infusions on the progressive ratio test in the IntA context than in the ShA context following 11 sessions. These results suggest that addiction-like behaviors following IntA self-administration may be influenced by context-specific learning factors.

Intermittent access training produces greater motivation for a non-drug reinforcer than long access training.

It has recently been proposed that the intermittent access (IntA) drug self-administration procedure better produces behavioral changes relevant to addiction than the long access (LgA) procedure. In this version of the IntA procedure, the drug is made available for a 5-min period during each half hour of a 6-h session. In contrast, on the LgA procedure, the drug is available continuously for 6 h. Previous studies have found that IntA drug self-administration produces greater drug motivation, measured by increased progressive ratio breakpoints, than LgA self-administration. It has been hypothesized that this effect is due to the rapid, "spiking" brain levels of the drug, and consequent neuroadaptations, experienced by rats during IntA sessions. However, no study has compared the effects of IntA versus LgA training on reinforcer motivation when using a non-drug reinforcer. The present study compared motivation for a saccharin reinforcer after IntA or LgA training. In Experiment 1, separate groups of rats lever-pressed for saccharin on the IntA or LgA procedures. In Experiment 2, a within-subjects design was used where rats pressed one lever on the IntA procedure and another lever on the LgA procedure for saccharin. In both experiments, IntA training produced greater breakpoints than LgA training. As no drug was used here, spiking drug levels could not have been responsible for the increased saccharin motivation observed after IntA training. Instead, it is proposed that differences in stimulus-reinforcer associations learned during IntA versus LgA training may be responsible for the effect. Future research is needed to determine the extent to which such learning factors may contribute to the increased motivation observed after IntA training with drug reinforcers.

Demand for fentanyl becomes inelastic following extended access to fentanyl vapor self-administration.

Opioid use disorder imposes great societal harm in the United States and in countries worldwide. Animal models that accurately capture motivational changes that occur in opioid dependence are critical to studying this disorder. The present study used a model of opioid vapor self-administration combined with a behavioral economics approach to determine whether rats would be more motivated to "work" to defend their baseline intake of fentanyl (i.e., more inelastic demand) following sufficiently frequent, intense, and chronic exposure to self-administered vaporized fentanyl. Male rats were allowed to respond for deliveries of 1.5-s of vaporized 10 mg/ml fentanyl solution. Following 15 sessions of short access (ShA; 1 h) vs. long access (LgA; 12 h) to self-administration, we conducted a between-sessions demand curve procedure, and observed significantly more inelastic demand for fentanyl (Essential Value; EV), and increased maximal response output (Omax) in LgA compared with ShA rats. In a subsequent phase, the unit-dose was doubled to 3 s of fentanyl vaporization. After seven ShA vs. LgA sessions, we assessed demand again and found that LgA rats, contrasted to ShA rats, demonstrated significantly higher baseline intake or "hedonic setpoint" (Q0), in addition to significantly increased EV and Omax. These results demonstrate that extended access to self-administration of a vaporized opioid causes changes in behavioral economic metrics consistent with development of an addiction-like state in rats. The combination of the vapor model with a translationally relevant behavioral economics framework opens new avenues to study dysregulated motivational processes in substance use disorders.

Heroin choice depends on income level and economy type.

RATIONALE: In a previous study, investigating choice between heroin and a non-drug alternative in animals and reductions in income (i.e., choices/day) caused the percentage of income spent on heroin to progressively decrease. In contrast, another study found that humans with opioid use disorder spent the majority of their income on heroin even though they had little income. Comparison of these two studies suggests that the seemingly conflicting results could be explained by differences in the underlying economy types of the choice alternatives. OBJECTIVE: The present experiment tested the hypothesis that the effect of income changes on choice between heroin and a non-drug alternative depends on economy type. METHODS: Rats chose between heroin and saccharin under three income levels. For the Closed group, the choice session was the only opportunity to obtain these reinforcers. For the Heroin Open group and the Saccharin Open group, choice sessions were followed by 3-h periods of unlimited access to heroin or saccharin, respectively. RESULTS: As income decreased, the Closed and Heroin Open groups, but not the Saccharin Open group, spent an increasingly greater percentage of income on saccharin than on heroin. The Saccharin Open group, compared to the other groups, spent a greater percentage of income on heroin as income decreased. CONCLUSIONS: Results confirm that the effects of income and economy type can interact and this may explain the apparently discrepant results of earlier studies. More generally, findings suggest that situations where heroin choice has little consequence for consumption of non-drug alternatives may promote heroin use.

Ad-libitum high fat diet consumption during adolescence and adulthood impacts the intravenous self-administration of cocaine in male Sprague-Dawley rats.

In preclinical populations, binge consumption of a high-fat diet (HFD) initiated during either adolescence or adulthood increases the intravenous self-administration (IVSA) of cocaine, whereas ad lib HFD consumption initiated during adulthood reduces or fails to influence cocaine intake. From this, it appears that binge exposure is a sufficient condition to increase cocaine IVSA and that such effects occur independent of the exposure period. It is not clear, however, if ad lib exposure would be sufficient to affect the IVSA of cocaine if initiated during adolescence, a developmental period associated with high-risk behavior. To investigate this question, the present experiment evaluated the effects of consumption of a HFD given throughout adolescence and adulthood on cocaine IVSA (0.75 mg/kg/infusion). Specifically, male Sprague-Dawley rats were maintained on either a HFD (n = 24) or chow diet (n = 15) beginning on postnatal day (PND) 21 and as adults underwent cocaine IVSA [Fixed Ratio (FR) 1, FR 5, FR 10, FR 20, Progressive Ratio (PR) and cue- and drug + cue-induced responding] from PNDs 77-126. Under all of these conditions, animals maintained on the HFD displayed higher rates of cocaine IVSA than those given access to chow. The present data demonstrate that under these specific conditions long-term exposure during the risk period of adolescence and extended throughout adulthood is capable of impacting the subsequent likelihood of cocaine self-administration and suggest that diet type and the duration of exposure may be important factors influencing the vulnerability to drug intake. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Ad libitum high fat diet consumption during adolescence and adulthood fails to impact the affective properties of cocaine in male Sprague-Dawley rats.

Recent research from our laboratories has demonstrated that long-term and ad libitum high fat diet (HFD) consumption during adolescence and adulthood increases the intravenous self-administration (IVSA) of cocaine in adult male Sprague-Dawley rats. One possible interpretation of these findings is that this dietary history influences the affective properties of cocaine, that is, cocaine's rewarding and/or aversive effects. In this context, our research and others suggest that the overall affective response to a drug, and its potential for use and abuse, reflects a balance between these properties in which the rewarding effects of a drug maintain its use and the aversive effects limit it. Accordingly, long-term HFD consumption might increase the rewarding effects of cocaine and/or decrease its aversive effects, resulting in greater IVSA. To examine this possibility, male Sprague-Dawley rats were maintained on either a HFD (n = 32) or chow diet (n = 32) beginning on postnatal day (PND) 21 and underwent combined cocaine-induced place preference and taste avoidance conditioning from PNDs 78-102. Under these conditions, cocaine (18 and 32 mg/kg, intraperitoneally [IP]), but not vehicle, was effective in inducing both a place preference and a taste avoidance; however, HFD- and chow-fed animals did not differ on either of these behavioral indices. These data suggest that the ability of ad libitum HFD consumption during adolescence to increase cocaine IVSA is not likely due to changes in the affective properties of cocaine. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Opening the cocaine economy by providing within-session access to a cheaper source of cocaine makes demand for it more elastic.

Previous studies found that opening the cocaine economy by providing postsession access to cocaine had no effect on animals' demand for cocaine, whereas postsession access to saccharin or food made demand for these nondrug reinforcers more elastic. It is possible that there was no effect of economy type on cocaine taking in these earlier studies because of the delay to the postsession cocaine in the open economy. The present experiment tested whether forming an open economy by providing additional within-session cocaine, rather than postsession cocaine, would make rats' demand for cocaine more elastic. Saccharin was used as a nondrug comparison reinforcer. Three groups of rats pressed one lever for cocaine and one for saccharin on an ascending series of fixed ratio (FR) schedules where the number of responses required per reinforcer increased from 1 to 48 over sessions. In the open cocaine and open saccharin economy groups, rats had occasional access during the session to a third lever where cocaine or saccharin reinforcers, respectively, were always available on an FR-1 schedule. The main finding was that demand for cocaine was more elastic in the open cocaine economy group than in either of the other groups. Demand for saccharin was more elastic in the open saccharin economy group than in the open cocaine economy group. This study shows that cocaine taking is sensitive to economy type when the additional source of cocaine in an open economy is available close in time to when rats work for cocaine.

Reduced ethanol self-administration in rats produced by the introduction of a high value non-drug alternative reinforcer.

Previous studies have shown that providing rats with a non-drug alternative in a choice situation can reduce ethanol taking in rats. There is also evidence that brief experience with non-drug reinforcers can reduce the reinforcing effects of drugs like cocaine, even when those non-drug alternatives are not pitted against the drug in a choice procedure. The goal of the present experiment was to determine whether experience with sucrose - a high value non-drug reinforcer in rats - in a non-choice situation would reduce ethanol's reinforcing effects, as measured within a behavioral economic framework. In a first phase, separate groups of rats worked on fixed-ratio schedules for ethanol, sucrose, or ethanol plus sucrose (during separate components within a session). In a second phase, all rats worked for ethanol and sucrose during alternating components. The introduction of sucrose components in the second phase to the group that previously only had experience with ethanol caused a significant decrease in ethanol self-administration. There was also a significant interaction whereby the effect of phase on the elasticity of demand for ethanol differed between the group that only had ethanol and the group that had ethanol plus sucrose in the first phase. These results indicate that a high value non-drug alternative reinforcer can reduce ethanol's reinforcing effects even when that alternative is not available at the time when ethanol is available. These findings suggest that treatments aiming to increase exposure to non-alcohol sources of reinforcement might be beneficial in reducing alcohol drinking.

The effect of economy type on heroin and saccharin essential value.

According to behavioral economics, reinforcer value should be lower in an open economy than in a closed economy. An animal model was used to determine how economy type affected the value of heroin and saccharin. In a first phase, separate groups of rats worked for heroin or saccharin. The price of these reinforcers increased over sessions. For rats in the open heroin or open saccharin economies, the work period of each session was followed by a postwork period where a cheaper source of heroin or saccharin was available for three hours. For rats in the closed economies, the work period was their only opportunity to obtain the reinforcer. Rats in the open saccharin economy worked less hard to defend consumption of saccharin as price increased than rats in the closed saccharin economy. That is, opening the saccharin economy reduced its essential value. In contrast, economy type had no effect on heroin's essential value. In a second phase, rats were allowed to choose between heroin and saccharin. The majority of rats strongly preferred saccharin over heroin regardless of economy type. The finding that economy type changed the essential value of saccharin, but not heroin, adds to previous findings suggesting that the value of drug reinforcers is unaffected by future drug availability. The difference in effect of economy type on drug versus nondrug reinforcers could be relevant to addiction. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The effect of economy type on reinforcer value.

This article reviews studies investigating the effect of economy type on reinforcer value. In a closed economy, consumption of the reinforcer depends entirely on the subject's behavior, whereas in an open economy it does not, due, for example, to the provision of free reinforcers after the session. In theory, reinforcers should have higher value in a closed economy than in an open economy. Experimental results relevant to this prediction and methods used to test economy type effects are summarized and discussed here. Studies have tested the effect of economy type on the value of a variety of reinforcers, including food, water, saccharin, various drugs, and video games. Subjects used have varied also and include humans, monkeys, rats, and mice. Whether economy type had an effect on reinforcer value appears to depend on the particular reinforcer studied and on the species used. In general, where there was a difference in reinforcer value across economies, the effect was consistent with the prediction that value should be lower in the open economy. In some studies, however, satiation across economy types may have been responsible for the difference, or at least contributed to it. Potential explanations for the economy type effect, including substitution of future reinforcers for current reinforcers, contingency degradation, anticipatory contrast, and optimal foraging, are discussed.

Like chimpanzees (Pan troglodytes), pigeons (Columba livia domestica) match and Nash equilibrate where humans (Homo sapiens) do not.

Martin, Bhui, Bossaerts, Matsuzawa, and Camerer (2014) found that chimpanzee pairs competing in matching-pennies games achieved the Nash equilibrium whereas human pairs did not. They hypothesized this outcome may be due to (a) chimpanzee ecology producing evolutionary changes that give them a cognitive advantage over humans in these games, and (b) humans being disadvantaged because the cognition necessary for optimal game play was traded off in evolution to support language. We provide data relevant to their hypotheses by exposing pairs of pigeons to the same games. Pigeons also achieved the Nash equilibrium, but did so while also conforming with the matching law prediction on concurrent schedules where choice ratios covary with reinforcer ratios. The cumulative effects model, which produces matching on concurrent schedules, also achieved the Nash equilibrium when it was simulated on matching-pennies games. The empirical and simulated compatibility between matching law and Nash equilibrium predictions can be explained in two ways. Choice to concurrent schedules, where matching obtains, and choice in game play, where the Nash equilibrium is achieved, may reflect the operation of a common process in choice (e.g., reinforcer maximization) for which matching and achieving the Nash equilibrium are derivative. Alternatively, if matching in choice is innate as some accounts argue, then achieving the Nash equilibrium may be an epiphenomenon of matching. Regardless, the wide species generality of matching relations in nonhuman choice suggests game play in chimpanzees would not prove advantaged relative to most species in the animal kingdom. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The effect of economy type on demand and preference for cocaine and saccharin in rats.

BACKGROUND: Economy type is an important determinant of reinforcer value. This study investigated the effect of open and closed economies on demand and preference for cocaine and saccharin in rats. METHODS: In the first phase, rats were trained to lever press for cocaine infusions or saccharin. The number of presses required for each reinforcer increased across sessions. Cocaine and saccharin economy type was manipulated over groups by varying post-session availability of these reinforcers. One group of rats had three hours' post-session access to unlimited cocaine (open economy). A second group had three hours' post-session access to unlimited saccharin. A third group had no post-session access to either reinforcer (closed economy). In a second phase, rats in the three conditions could make mutually exclusive choices for cocaine or saccharin. RESULTS: Post-session access to saccharin caused saccharin demand to become more elastic. Post-session access to cocaine had no effect on demand for cocaine but made demand for saccharin more elastic. Results from the choice phase generally paralleled those from the demand phase, the main finding being that post-session saccharin access caused an increase in cocaine preference. CONCLUSIONS: These results show that manipulating economy type can affect cocaine and non-drug reinforcers differently. Opening the saccharin economy decreased saccharin's value. Opening the cocaine economy did not decrease cocaine's value, but instead led to a devaluation of saccharin. These results suggest that cocaine choice may be determined not only by the reinforcers immediately available, but also by those reinforcers' broader contexts of availability.

Does a rat free a trapped rat due to empathy or for sociality?

This report evaluates whether a rat releasing a trapped rat from a restraint tube is better explained as due to its empathic motivation or to the pursuit of social contact. In the first condition, each of six rats chose in an E maze between entering an empty goal box versus entering a goal box where its entrance caused a rat trapped in a restraint tube to be released. Rats preferred the goal box with the trapped rat over the empty goal box. In the second condition, these rats chose between releasing a restraint-tube-trapped rat in one goal box and another rat in the second goal box that was not locked into its restraint tube. Rats showed no preference between alternatives. In the third condition, rats chose between a goal box containing a rat with an open restraint tube and an empty goal box. Rats preferred the rat with the open restraint tube over the empty goal box. These results support attributing the response of releasing a rat from a restraint tube to the reinforcing power of social contact rather than interpreting this response as empathically motivated.

Cocaine impairs serial-feature negative learning and blood-brain barrier integrity.

Previous research has shown that diets high in fat and sugar [a.k.a., Western diets (WD)] can impair performance of rats on hippocampal-dependent learning and memory problems, an effect that is accompanied by selective increases in hippocampal blood brain barrier (BBB) permeability. Based on these types of findings, it has been proposed that overeating of a WD (and its resulting obesity) may be, in part, a consequence of impairments in these anatomical substrates and cognitive processes. Given that drug use (and addiction) represents another behavioral excess, the present experiments assessed if similar outcomes might occur with drug exposure by evaluating the effects of cocaine administration on hippocampal-dependent memory and on the integrity of the BBB. Experiment 1 of the present series of studies found that systemic cocaine administration in rats also appears to have disruptive effects on the same hippocampal-dependent learning and memory mechanism that has been proposed to underlie the inhibition of food intake. Experiment 2 demonstrated that the same regimen of cocaine exposure that produced disruptions in learning and memory in Experiment 1 also produced increased BBB permeability in the hippocampus, but not in the striatum. Although the predominant focus of previous research investigating the etiologies of substance use and abuse has been on the brain circuits that underlie the motivational properties of drugs, the current investigation implicates the possible involvement of hippocampal memory systems in such behaviors. It is important to note that these positions are not mutually exclusive and that neuroadaptations in these two circuits might occur in parallel that generate dysregulated drug use in a manner similar to that of excessive eating.