Repeated Δ-9-Tetrahydrocannabinol administration dose dependently increases stablished schedule-induced drinking.

RATIONALE: Schedule-induced drinking (SID) reproduces an excessive and repetitive behavioural pattern that has led to propose this procedure as an animal model to study compulsive behaviours. Although it is known that cannabis can cause several adverse effects, in recent years there has been great interest in the medical application of cannabis derivatives for obsessive-compulsive related disorders. OBJECTIVES: The present study investigated the effects of repeated THC administration on rates of previously acquired SID, as well as the possible alteration of its temporal distribution along inter-food intervals. METHODS: Male Wistar rats acquired SID under a 30 min fixed-time 30-sec food delivery schedule (from 30 to 43 sessions to reach a stable level). Thereafter, 5 or 10 mg/kg daily i.p. injections of THC or vehicle were repeatedly administered for 7 days to evaluate the effects on SID. RESULTS: Repeated THC administration at a dose of 5 mg/kg resulted in an increase on licking. Surprisingly, no effects on SID were observed with the 10 mg/kg dose. However, magazine entries were reduced with both THC doses. THC also modified the temporal distributions of licking and magazine entries during inter-food intervals. CONCLUSIONS: The present results show that repeated THC administration may (i) increase induced licking at moderate doses, (ii) reduce magazine entries, and (iii) affect the temporal pattern of SID. These findings suggest that THC does not appear to be beneficial to reduce compulsive behaviour in this animal model, while another collateral effect of THC -such as a greater habitual-like behaviour- needs to be considered.

Environmental enrichment accelerates the acquisition of schedule-induced drinking in rats.

Environmental enrichment (EE) provides an improvement in the housing conditions of experimental animals, such as laboratory rats, with greater physical and social stimulation through toys and company in the home cages. Its use is known to influence performance of experimental protocols, but these effects have not been well determined in the schedule-induced drinking (SID) procedure. The main goal of this study was to investigate the effects of EE on the acquisition of SID in 24 12-week-old male Wistar rats, divided into two groups, a group with EE housed with toys and companions, and a group without enrichment in individual housing conditions without toys (social isolation and no environmental enrichment, INEE). A total of 25 sessions, under a fixed time 30 s food reinforcement schedule and with access to water in the experimental chambers were carried out. Sessions lasted 30 min. The results showed that the EE group developed faster the excessive drinking pattern of SID, and drank to higher levels, than the INEE group. The greater development of SID in the EE group contradicts the view of schedule-induced behavior as linked to stress reduction and better suits with the conception of induction related to positive reinforcement.

Schedule-induced alcohol intake during adolescence sex dependently impairs hippocampal synaptic plasticity and spatial memory.

In a previous study, we demonstrated that intermittent ethanol administration in male adolescent animals impaired hippocampus-dependent spatial memory, particularly under conditions of excessive ethanol administration. In this current study, we subjected adolescent male and female Wistar rats an alcohol schedule-induced drinking (SID) procedure to obtain an elevated rate of alcohol self-administration and assessed their hippocampus-dependent spatial memory. We also studied hippocampal synaptic transmission and plasticity, as well as the expression levels of several genes involved in these mechanisms. Both male and female rats exhibited similar drinking patterns throughout the sessions of the SID protocol reaching similar blood alcohol levels in all the groups. However, only male rats that consumed alcohol showed spatial memory deficits which correlated with inhibition of hippocampal synaptic plasticity as long-term potentiation. In contrast, alcohol did not modify hippocampal gene expression of AMPA and NMDA glutamate receptor subunits, although there are differences in the expression levels of several genes relevant to synaptic plasticity mechanisms underlying learning and memory processes, related to alcohol consumption as Ephb2, sex differences as Pi3k or the interaction of both factors such as Pten. In conclusion, elevated alcohol intake during adolescence seems to have a negative impact on spatial memory and hippocampal synaptic plasticity in a sex dependent manner, even both sexes exhibit similar blood alcohol concentrations and drinking patterns.

Socialization, and its modulation by sex, on the development and recovery of activity-based anorexia in rats.

The activity-based anorexia (ABA) animal model has been used in the laboratory to study the role of excessive physical activity in the manifestation of anorexia nervosa (AN) in humans. Factors of social context are crucial in human health and the emergence of many psychological disorders, which have also been observed in studies using different mammal species that, like human beings, set their lives in groups. In the present study, the animals' social condition was manipulated to observe the effect of socialization in ABA development, and the possible different influence of the variable sex on the phenomenon. Eighty Wistar Han rats were distributed into four male and four female groups with 10 subjects each, manipulating social conditions (group housing or social isolation) and physical activity (access or not to a running wheel). Throughout the procedure, all groups had food restricted to 1 h/day during the light period. Furthermore, ABA experimental groups with access to the running wheel had two periods of access to the wheel of 2 h each, one before and the other after the food period. In this experiment, socialized rats were less vulnerable to weight loss during the procedure, although there were no differences between the ABA groups. Moreover, social enrichment was shown to be an enabling variable of the animals' recovery after their withdrawal from the procedure, with this effect being more pronounced in females. The results in this study suggest the need to further in the analysis of the role of socialization in the development of ABA.

Mutual facilitation between activity-based anorexia and schedule-induced polydipsia in rats.

The objective of this study was to evaluate the possible relationship between drinking (licks) in the schedule-induced polydipsia (SIP) phenomenon and running (turns in the wheel) in the activity-based anorexia (ABA) one. Within-subjects counterbalanced experiments were designed with male Wistar rats which underwent both behavioral procedures; half of them performed the ABA procedure first and the other half the SIP procedure first. In Experiment 1, the initial development of ABA facilitated the subsequent acquisition of SIP, whereas the first acquisition of SIP retarded the subsequent development of ABA. Given that SIP exposure implied food restriction, it could be that adaptation to the food regime contributed to lowering ABA manifestation. Thus, Experiment 2 was carried out in exactly the same way as Experiment 1, with the exception that animals which first went through SIP prior to undergoing the ABA procedure had no food restriction. In this case, both ABA and SIP as first experiences facilitated the further development of SIP and ABA, respectively. This suggests that running in ABA may be functionally similar to drinking in SIP; therefore, both behaviors can be thought of as induced by the schedule/regime of intermittent food availability.

Physical activity reduces alcohol consumption induced by reward downshift.

Increased voluntary consumption of alcohol and other anxiolytics has been demonstrated in animals after experiencing frustrative reward devaluation (downshift) or omission. These results have been interpreted in terms of emotional self-medication. In the present study, we analyzed whether voluntary physical activity reduces alcohol intake induced by reward downshift. Sixty-four male Wistar rats were divided into eight groups (n = 8). Thirty-two (downshifted) animals received 32% sucrose during 10 preshift sessions (5 min), followed by 4% sucrose during five postshift sessions, whereas 32 (unshifted) controls were always exposed to 4% sucrose. Immediately after each consummatory session, animals were exposed to a 2-hr two-bottle preference test involving 32% alcohol versus water or water versus water. Half of the animals had also access to a wheel for voluntary running during the preference test. The results showed lower sucrose consumption in downshifted groups compared with unshifted controls (the frustrative reward downshift effect). Reward downshift significantly increased alcohol intake, this effect being absent in downshifted animals with access to the wheel. These findings suggest that physical exercise could be useful to prevent alcohol self-medication induced by frustrative nonreward. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Activity-based anorexia alters hypothalamic POMC and orexin populations in male rats.

The objective of this study was to investigate the orexin and POMC populations in the hypothalamic nuclei of male Wistar rats after the activity-based anorexia (ABA) procedure. Four groups were established based on food restriction and activity: activity (A), ABA, diet (D) and control (C). The ABA protocol consisted of free access to a running wheel for a period of 22 h and access to food for 1 h. When the animals in the ABA group reached the ABA criterion, were sacrificed, and their brains were collected and serially sectioned. The free-floating sections were processed for orexin and POMC immunostaining. The number of orexin A-ir cells in the perifornical-dorsomedial-hypothalamus continuum (PFD) and lateral hypothalamus (LH) and the number of POMC-ir cells in the arcuate nucleus (Arc) were estimated. Data on food intake, body weight and wheel turns were also analyzed. The ABA procedure caused a significant decrease in body weight along with a significant increase in activity. Moreover, at the end of the ABA procedure, the number of POMC-ir cells decreased in the Arc in the A group, and significantly more in the ABA group, and the number of orexin A-ir positive cells decreased in the LH in D and ABA groups. The differential decrease in POMC in the ABA group emphasizes the importance of the melanocortin system in the maintenance of ABA, but more research is needed to elucidate the involvement of this peptide in the mechanism that promotes and maintains anorexia nervosa and how increased activity may interact with all these processes.

Influence of early maternal separation on susceptibility to the activity-based anorexia model in male and female Sprague Dawley rats.

A principal animal paradigm employed in Anorexia Nervosa (AN) study is the activity-based anorexia (ABA) model. The model's efficacy in recapitulating the core features of AN in humans allows for the study of the parameters involved in the disorder. The current study examined the susceptibility to the ABA protocol in the presence of a significant stressor (maternal separation) in male and female Sprague Dawley rats. More importantly, we analysed the sex-differences on activity levels during different periods of the ABA protocol to determine the period(s) influencing the most pathological weight loss. Both components of the ABA protocol contributed to the subjects' bodyweight loss. Stress in the first two weeks of development conferred a protective effect in males. Time spent and activity levels on the running wheel were higher in females compared to males. Hyperactivity in ABA subjects was observed during the food-anticipatory activity (FAA) and postprandial activity in males and during the FAA and nocturnal activity periods in females. This study aids in understanding the effect of intensity of activity during specific periods on the pathological weight loss in ABA rats. These observations are informative for therapies aimed at ameliorating body mass index in AN patients.

Chronic ∆-9-tetrahydrocannabinol administration delays acquisition of schedule-induced drinking in rats and retains long-lasting effects.

RATIONALE: Schedule-induced drinking (SID) is a behavioural phenomenon characterized by an excessive and repetitive drinking pattern with a distinctive temporal distribution that has been proposed as a robust and replicable animal model of compulsivity. Despite cannabis currently being the most widely consumed illicit drug, with growing interest in its clinical applications, little is known about the effects of ∆-9-tetrahydrocannabinol (THC) on SID. OBJECTIVES: The effects of chronic and acute THC administration on SID acquisition, maintenance and extinction were studied, as were the effects of such administrations on the distinctive temporal distribution pattern of SID. METHODS: THC (5 mg/kg i.p.), or the corresponding vehicle, was administered to adult Wistar rats for 14 days in a row. Subsequently, THC effects on SID acquisition were tested during 21 sessions using a 1-h fixed-time 60-s food delivery schedule. Acute effects of THC were also evaluated after SID development. Finally, two extinction sessions were conducted to assess behavioural persistence. RESULTS: The results showed that previous chronic THC treatment delayed SID acquisition and altered the distinctive behavioural temporal distribution pattern during sessions. Moreover, acute THC administration after SID development decreased SID performance in animals chronically pre-treated with the drug. No great persistence effects were observed during extinction in animals pre-treated with THC. CONCLUSIONS: These results suggest that chronic THC affects SID development, confirming that it can disrupt learning, possibly causing alterations in time estimation, and also leads to animals being sensitized when they are re-exposed to the drug after long periods without drug exposure.

Assessment of the 'timing' function of schedule-induced behavior on fixed-interval performance.

It has been suggested that schedule-induced behaviors allow organisms to adapt better to temporal regularities of the environment. The main goal of the present study was to observe the effect of schedule-induced drinking (SID) on the performance in fixed-interval (FI) schedules. Rats were exposed to a FI 15-, 30-, or 60-s food reinforcement schedule, and only half of them had access to water in the experimental chamber. Rats with access to water developed SID, which occurred in the first part of the interval, regardless of the FI value, and was followed by an increase in lever pressing rate. There were no substantial differences in the quantitative measures of timing between groups that had or did not have access to water, except for the rats in the FI 15-s group with access to water, who showed longer postreinforcement pauses, possibly attributable to competition between SID and lever pressing. SID did not manifest the scalar property, contrary to lever pressing, but it is proposed that behaviors are displayed serially until the last behavior before the target operant response becomes a discriminative stimulus for that behavior. It is not assumed that the purpose of schedule-induced behaviors is to aid timing, but the development of behavioral patterns might determine the performance of organisms on temporal tasks. Additionally, in some cases competition between responses might exert more control on when the operant behavior occurs than timing. Timing seems to consist in the temporal organization of available behaviors that leads to a specific behavior occurring at a specified time, a single characteristic that typically had come to indicate accurate timing. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The irrelevancy of the inter-trial interval in delay-discounting experiments on an animal model of ADHD.

Delay discounting involves choosing between a small, immediate reward, and a larger but delayed one. As the delay between choice and large reward gets longer, people with ADHD tend to become impulsive faster than controls, indicated by a switch in preference from the large to the smaller reward. Choosing the smaller reward when the larger is considered reward maximizing is labeled impulsive behaviour. It is well documented that increased delays between choice and reward affects choice preference in both humans and other animals. Other variables such as the inter-trial interval or trial length are observed to have an effect on human discounting, but their effect on discounting in other animals is largely assumed rather than tested. In the current experiment, we tested this assumption. One group of rats was exposed to increasing delays between choosing the large reward and receiving it, while another group experienced longer inter-trial intervals that were equal in length to the delays in the other group. This ensured that trial length was controlled for in delay discounting, but that the delay function and inter-trial intervals could be manipulated and measured separately. Results showed that while the delay between choice and reward caused impulsive behaviour in rats, the length of the inter-trial interval (and by extension trial length) had no impact on choice behaviour. A follow-up experiment found this to be the case even if the length of the inter-trial interval was signaled with audio cues. These results suggest that rats, and possibly animals in general, are insensitive to time between trials, and therefore cannot easily represent human counterparts on the task.

Static internal representation of dynamic situations reveals time compaction in human cognition.

INTRODUCTION: The human brain has evolved under the constraint of survival in complex dynamic situations. It makes fast and reliable decisions based on internal representations of the environment. Whereas neural mechanisms involved in the internal representation of space are becoming known, entire spatiotemporal cognition remains a challenge. Growing experimental evidence suggests that brain mechanisms devoted to spatial cognition may also participate in spatiotemporal information processing. OBJECTIVES: The time compaction hypothesis postulates that the brain represents both static and dynamic situations as purely static maps. Such an internal reduction of the external complexity allows humans to process time-changing situations in real-time efficiently. According to time compaction, there may be a deep inner similarity between the representation of conventional static and dynamic visual stimuli. Here, we test the hypothesis and report the first experimental evidence of time compaction in humans. METHODS: We engaged human subjects in a discrimination-learning task consisting in the classification of static and dynamic visual stimuli. When there was a hidden correspondence between static and dynamic stimuli due to time compaction, the learning performance was expected to be modulated. We studied such a modulation experimentally and by a computational model. RESULTS: The collected data validated the predicted learning modulation and confirmed that time compaction is a salient cognitive strategy adopted by the human brain to process time-changing situations. Mathematical modelling supported the finding. We also revealed that men are more prone to exploit time compaction in accordance with the context of the hypothesis as a cognitive basis for survival. CONCLUSIONS: The static internal representation of dynamic situations is a human cognitive mechanism involved in decision-making and strategy planning to cope with time-changing environments. The finding opens a new venue to understand how humans efficiently interact with our dynamic world and thrive in nature.

A View on the Development and Current Situation of Behavior Analysis in Europe.

The present article discusses essential historical trends in behavior analysis in Europe, in terms of both organizations and conferences. Of particular interest is the series of the European Meetings on the Experimental Analysis of Behaviour held in different European cities between 1983 and 2000, just when the European Association for Behaviour Analysis (EABA) and the European Journal of Behavior Analysis (EJOBA) both started. This article not only extends the information on EABA and EJOBA from a previous publication (Arntzen et al., 2009) but also discusses other European behavior-analytic outlets and different ways in which behavior analysis is taught in Europe.

Effects of partial reinforcement on autoshaping in inbred Roman high- and low-avoidance rats.

Individuals trained under partial reinforcement (PR) typically show a greater resistance to extinction than individuals exposed to continuous reinforcement (CR). This phenomenon is referred to as the PR extinction effect (PREE) and is interpreted as a consequence of uncertainty-induced frustration counterconditioning. In this study, we assessed the effects of PR and CR in acquisition and extinction in two strains of rats, the inbred Roman high- and low-avoidance (RHA and RLA, respectively) rats. These two strains mainly differ in the expression of anxiety, the RLA rats showing more anxiety-related behaviors (hence, more sensitive to frustration) than the RHA rats. At a neurobiological level, mild stress is known to elevate corticosterone in RLA rats and dopamine in RHA rats. We tested four groups of rats (RHA/CR, RHA/PR, RLA/CR, and RLA/PR) in two successive acquisition-extinction phases to try to consolidate the behavioral effects. Animals received training in a Pavlovian autoshaping procedure with retractable levers as the conditioned stimulus, food pellets as the unconditioned stimulus, and lever presses as the conditioned response. In Phase 1, we observed a PREE in lever pressing in both strains, but this effect was larger and longer lasting in RHA/PR than in RLA/PR rats. In Phase 2, reacquisition was fast and the PREE persisted in both strains, although the two PR groups no longer differed in lever pressing. The results are discussed in terms of frustration theory and of uncertainty-induced sensitization of dopaminergic neurons.

Behavior Stability and Individual Differences in Pavlovian Extended Conditioning.

How stable and general is behavior once maximum learning is reached? To answer this question and understand post-acquisition behavior and its related individual differences, we propose a psychological principle that naturally extends associative models of Pavlovian conditioning to a dynamical oscillatory model where subjects have a greater memory capacity than usually postulated, but with greater forecast uncertainty. This results in a greater resistance to learning in the first few sessions followed by an over-optimal response peak and a sequence of progressively damped response oscillations. We detected the first peak and trough of the new learning curve in our data, but their dispersion was too large to also check the presence of oscillations with smaller amplitude. We ran an unusually long experiment with 32 rats over 3,960 trials, where we excluded habituation and other well-known phenomena as sources of variability in the subjects' performance. Using the data of this and another Pavlovian experiment by Harris et al. (2015), as an illustration of the principle we tested the theory against the basic associative single-cue Rescorla-Wagner (RW) model. We found evidence that the RW model is the best non-linear regression to data only for a minority of the subjects, while its dynamical extension can explain the almost totality of data with strong to very strong evidence. Finally, an analysis of short-scale fluctuations of individual responses showed that they are described by random white noise, in contrast with the colored-noise findings in human performance.

Effect of Schedule-Induced Behavior on Responses of Spontaneously Hypertensive and Wistar-Kyoto Rats in a Delay-Discounting Task: A Preliminary Report.

Delay discounting is the loss of the subjective value of an outcome as the time to its delivery increases. It has been suggested that organisms can become more tolerant of this delay when engaging in schedule-induced behaviors. Schedule-induced behaviors are those that develop at a high rate during intermittent reinforcement schedules without the need of arranged contingency to the reinforcer, and they have been considered as a model of compulsivity. There is evidence that relates compulsivity to greater delay discounting. The rate of delay discounting represents how impulsive the subject is, as the rate of discounting increases the higher the impulsivity. Thus, the main purpose of this study was to undertake a preliminary evaluation of whether developing schedule-induced behaviors affects performance in a delay-discounting task, by comparing spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. The rats were exposed to a task that consisted of presenting the subjects with two levers: one produced a small, immediate food reinforcer while the other one produced a larger, delayed reinforcer. During Condition A, the levers were presented, and a water bottle and a running wheel were available in the conditioning chambers; during Condition B, only the levers were presented. SHR and WKY rats developed schedule-induced behaviors during Condition A and showed no difference in discounting rates, contradicting previous reports. Lick allocation during response-reinforcer delays and the inter-trial interval (ITI) showed, respectively, pre- and post-food distributions. Discounting rates during Condition B (when rats could not engage in schedule-induced behaviors) did not reach statistical significance difference among strains of animals, although it was observed a tendency for WKY to behave more self-controlled. Likewise it was not found any effect of schedule-induced behavior on discounting rates, however, a tendency for WKY rats to behave more impulsive during access to drink and run seems to tentatively support the idea of schedule-induced behavior as a model of compulsivity in those rats, being impulsivity simply defined as an excess in behavior.

Exercise, diet, and the reinforcing value of food in an animal model of anorexia nervosa.

Activity-based anorexia (ABA) develops when laboratory rats are subjected to a single meal per day and have access to an activity wheel for the remaining time. Here, we studied the contribution of exercise and diet to the reinforcing value of food during ABA development. Three groups of eight adult male Wistar rats were used: an ABA group with 21.5 hr (then 22 hr) of wheel access and 1 hr (then 30 min) of food access, a control group with the same time exposure to food but without exercise, and a yoked group to the ABA in terms of weight loss. Rats were daily tested on a progressive-ratio schedule to measure their motivation for food. ABA rats gradually reduced their body weight more than the food control group. Animals steadily increased their breaking points in parallel to losses in body weight, but no significant differences were found between groups. Adult rats can develop ABA, but their loss in weight neither resulted in a decrease of food intake nor in the motivation to obtain it.

The Effect of Methylphenidate on the Microstructure of Schedule-Induced Polydipsia in an animal model of ADHD.

Schedule-induced polydipsia (SIP) was established in spontaneously hypertensive rats (SHR), Wistar Kyoto rats (WKY), and Wistar rats, using a multiple fixed-time (FT) schedule of food delivery, with 30- and 90-s components. Thereafter, animals were exposed to methylphenidate (MPH; 2.5mg/kg/d) for six consecutive SIP sessions. A test to assess possible sensitization effects was also conducted four days after termination of the drug treatment. At baseline, FT 90-s produced longer and more frequent drinking episodes in SHR than in WKY. An analysis of the distribution of inter-lick intervals revealed that drinking was organized in bouts, which were shorter in SHR than in WKY. Across strains and schedules, MPH shifted drinking episodes towards the beginning of inter-food intervals, which may reflect a stimulant effect on SIP. MPH transiently reduced the frequency of drinking episodes in WKY in FT 30-s, and more permanently reduced the frequency of licking bouts in Wistar rats. MPH also increased the length of licking bouts in Wistar rats. Overall, SHR displayed a hyperactive-like pattern of drinking (frequent but short bouts), which 2.5mg/kg MPH appears to reduce in WKY and Wistar but not in SHR rats. It appears that therapeutic effects of MPH on hyperactive-like SIP require higher doses in SHR relative to control strains.

Effects of dopamine agents on a schedule-induced polydipsia procedure in the spontaneously hypertensive rat and in Wistar control rats.

The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attention deficit hyperactivity disorder (ADHD), and typically develops excessive patterns of response under most behavioural protocols. Schedule-induced polydipsia (SIP) is the excessive water consumption that occurs as a schedule effect when food is intermittently delivered and animals are partially food- but not water-deprived. SIP has been used as a model of excessive behaviour, and considerable evidence has involved the dopaminergic system in its development and maintenance. The aim of this study was to evaluate the effects of the most common psychostimulants used in ADHD treatment on SIP, comparing their effects in SHRs with rats from control populations. SHR, Wistar Kyoto (WKY) and Wistar rats were submitted to a multiple fixed time (FT) food schedule with two components: 30 s and 90 s. The acute effects of different dopaminergic compounds were evaluated after 40 sessions of SIP acquisition. All animals showed higher adjunctive drinking under FT 30 s than FT 90 s, and SHRs displayed higher asymptotic SIP levels in FT 90 s compared to WKY and Wistar rats. SHRs were less sensitive to dopaminergic agents than control rats in terms of affecting rates of adjunctive drinking. These differences point to an altered dopaminergic system in the SHR and provide new insights into the neurobiological basis of ADHD pharmacological treatments.