Variable-interval Schedules Research Articles

Toward a Procedure to Study Rule-Governed Choice: Preliminary Data

AbstractThe aim of this study was to model a situation that induced choice between following two incompatible rules, each associated with a different rate of reinforcement. In Experiment 1, eight undergraduate students were exposed to a two-component multiple schedule (training). In each component, there was a concurrent variable interval (VI)–extinction (EXT) schedule. Participants were given two rules that instructed them to respond to the VI alternative in the presence of different discriminative stimuli. The side of the VI schedule changed in each component and offered a different reinforcer rate according to the discriminative stimuli in the operation. When both discriminative stimuli were concurrently presented (test), participants favored the alternative previously instructed by the rule, which was associated with the greatest reinforcer rate, whereas indifference was observed in the absence of discriminative stimuli. Experiment 2 tested the effects of reinforcement rate using the same procedure without providing rules. During training, participants gradually developed a preference for the VI alternatives. In the choice test phase, participants favored the alternative associated with the stimuli with the highest reinforcer rate when both discriminative stimuli were present. Unsystematic preference was observed in the absence of discriminative stimuli. Two alternative explanations were provided for the findings.

Hyperbolae.

Hyperbolic relations between independent and dependent variables are ubiquitous in the experimental analysis of behavior, mentioned in over 150 articles in the Journal of the Experimental Analysis of Behavior. There are two principal forms of hyperbolae: The first describes the relation between response rate and reinforcement rate on variable-interval schedules of reinforcement; it rises asymptotically toward a maximum. The second describes the relation between the current equivalent value of an incentive and its delay or (im)probability; it falls from a maximum toward an asymptote of 0. Where do these come from? What do their parameters mean? How are they related? This article answers the first two questions and addresses the last.

The active time model of concurrent choice.

The following paper describes a steady-state model of concurrent choice, termed the active time model (ATM). ATM is derived from maximization principles and is characterized by a semi-Markov process. The model proposes that the controlling stimulus in concurrent variable-interval (VI) VI schedules of reinforcement is the time interval since the most recent response, termed here "the active interresponse time" or simply "active time." In the model after a response is generated, it is categorized by a function that relates active times to switch/stay probabilities. In the paper the output of ATM is compared with predictions made by three other models of operant conditioning: melioration, a version of scalar expectancy theory (SET), and momentary maximization. Data sets considered include preferences in multiple-concurrent VI VI schedules, molecular choice patterns, correlations between switching and perseveration, and molar choice proportions. It is shown that ATM can account for all of these data sets, while the other models produce more limited fits. However, rather than argue that ATM is the singular model for concurrent VI VI choice, a consideration of its concept space leads to the conclusion that operant choice is multiply-determined, and that an adaptive viewpoint-one that considers experimental procedures both as selecting mechanisms for animal choice as well as tests of the controlling variables of that choice-is warranted.

How do animals weigh conflicting information about reward sources over time? Comparing dynamic averaging models

Optimal foraging theory suggests that animals make decisions which maximize their food intake per unit time when foraging, but the mechanisms animals use to track the value of behavioral alternatives and choose between them remain unclear. Several models for how animals integrate past experience have been suggested. However, these models make differential predictions for the occurrence of spontaneous recovery of choice: a behavioral phenomenon in which a hiatus from the experimental environment results in animals reverting to a behavioral allocation consistent with a reward distribution from the more distant past, rather than one consistent with their most recently experienced distribution. To explore this phenomenon and compare these models, three free-operant experiments with rats were conducted using a serial reversal design. In Phase 1, two responses (A and B) were baited with pellets on concurrent variable interval schedules, favoring option A. In Phase 2, lever baiting was reversed to favor option B. Rats then entered a delay period, where they were maintained at weight in their home cages and no experimental sessions took place. Following this delay, preference was assessed using initial responding in test sessions where levers were presented, but not baited. Models were compared in performance, including an exponentially weighted moving average, the Temporal Weighting Rule, and variants of these models. While the data provided strong evidence of spontaneous recovery of choice, the form and extent of recovery was inconsistent with the models under investigation. Potential interpretations are discussed in relation to both the decision rule and valuation functions employed.

The temporal structure of goal-directed and habitual operant behavior.

Operant behavior can reflect the influence of goal-directed and habitual processes. These can be distinguished by changes to response rate following devaluation of the reinforcing outcome. Whether a response is goal directed or habitual depends on whether devaluation affects response rate. Response rate can be decomposed into frequencies of bouts and pauses by analyzing the distribution of interresponse times. This study sought to characterize goal-directed and habitual behaviors in terms of bout-initiation rate, within-bout response rate, bout length, and bout duration. Data were taken from three published studies that compared sensitivity to devaluation following brief and extended training with variable-interval schedules. Analyses focused on goal-directed and habitual responding, a comparison of a habitual response to a similarly trained response that had been converted back to goal-directed status after a surprising event, and a demonstration of contextual control of habit and goal direction in the same subjects. Across experiments and despite responses being clearly distinguished as goal directed and habitual by total response rate, analyses of bout-initiation rate, within-bout rate, bout length, and bout duration did not reveal a pattern that distinguished goal-directed from habitual responding.

Knockout of NMDARs in CA1 and dentate gyrus fails to impair temporal control of conditioned behavior in mice.

The hippocampus has been implicated in temporal learning. Plasticity within the hippocampus requires NMDA receptor-dependent glutamatergic neurotransmission. We tested the prediction that hippocampal NMDA receptors are required for learning about time by testing mice that lack postembryonal NMDARs in the CA1 and dentate gyrus (DG) hippocampal subfields on three different appetitive temporal learning procedures. The conditional knockout mice (Grin1ΔDCA1 ) showed normal sensitivity to cue duration, responding at a higher level to a short duration cue than compared to a long duration cue. Knockout mice also showed normal precision and accuracy of response timing in the peak procedure in which reinforcement occurred after 10 s delay within a 30 s cue presentation. Mice were tested on the matching of response rates to reinforcement rates on instrumental conditioning with two levers reinforced on a concurrent variable interval schedule. Pressing on one lever was reinforced at a higher rate than the other lever. Grin1ΔDGCA1 mice showed normal sensitivity to the relative reinforcement rates of the levers. In contrast to the lack of effect of hippocampal NMDAR deletion on measures of temporal sensitivity, Grin1ΔDGCA1 mice showed increased baseline measures of magazine activity and lever pressing. Furthermore, reversal learning was enhanced when the reward contingencies were switched in the lever pressing task, but this was true only for mice trained with a large difference between relative reinforcement rates between the levers. The results failed to demonstrate a role for NMDARs in excitatory CA1 and DG neurons in learning about temporal information.

Coordinated and individual responding in pairs of rats under variable interval schedules

The coordination of responses in pairs of rats was investigated by parametrically manipulating the duration of variable-interval (VI) schedule mean inter-reinforcer intervals (IRIs). Two conditions required coordination for a group of three pairs of rats (VI 5 s, 10 s, 20 s, 40 s, 80 s, 120 s, 160 s, 60 s, and 243 s) and individual responding for another group of three pairs of rats (VI 5, 10 s, 20 s, 40 s and 80 s). An inverted U-shaped function related responding measures and reinforcement rates: Overall response rates, coordinated episode rates and percentage of coordination increased with increasing reinforcement rates, and decreased at the highest rates of reinforcement in both groups. Rats exposed to VI schedules that required coordination generally showed higher rates and higher percentages of coordinated responses when compared to rats that responded under the individual schedules. Local rates of coordinated episodes showed that coordination occurred at a steady rate across the VI IRIs for the Coordination Group. The results extend previous research on the patterns of coordinated responses maintained by intermittent schedules of reinforcement.

Assessing attention and impulsivity in the variable stimulus duration and variable intertrial interval rodent continuous performance test schedules using dopamine receptor antagonists in female C57BL/6JRj mice

RationaleDopaminergic dysfunction is implicated in disorders of impulsivity and inattention. The rodent continuous performance test (rCPT) has been used to quantify changes in attention and impulsivity.ObjectiveTo examine the roles of dopamine receptors in attention and impulsivity behaviours measured in the rCPT variable stimulus duration (vSD) and the variable intertrial interval schedules (vITI) using DA receptor antagonists.MethodsTwo cohorts of 35 and 36 female C57BL/6JRj mice were examined separately in the rCPT, vSD, and vITI schedules, respectively. Both cohorts received antagonists of the following receptors: D1/5 (SCH23390, SCH: 0.01, 0.02, 0.04 mg/kg) and D2/3 (raclopride, RAC 0.03, 0.10, 0.30 mg/kg) in consecutive balanced Latin square designs with flanking reference measurements. The antagonists were subsequently examined for effects on locomotor activity.ResultsSCH showed similar effects in both schedules, and the effects were reference-dependent in the vITI schedule. SCH reduced responding, but improved response accuracy, impulsivity, discriminability, and locomotor activity. RAC showed mixed effects on responsivity, but improved accuracy and discriminability. The discriminability improvement was driven by an increase in hit rate in the vITI schedule and a reduction in false alarm rate in the vSD schedule. RAC also decreased locomotor activity.ConclusionBoth D1/5 and D2/3 receptor antagonism reduced responding, but the outcome on discriminability differed, stemming from individual effects on hit and false alarm rate, and the weight of omissions within the calculation. The effects of SCH and RAC suggest that endogenous DA increases responding and impulsivity, but reduces accuracy and shows mixed effects on discriminability.

Assessing attention and impulsivity in the variable stimulus duration and variable intertrial interval rodent continuous performance test schedules using noradrenaline receptor antagonists in female C57BL/6JRj mice

RationaleNoradrenergic dysfunction is associated with disorders of impulsivity and inattention. The rodent continuous performance test (rCPT) quantifies changes in attention and impulsivity.ObjectiveTo use NA receptor antagonists to examine the roles of NA on attention and impulsivity behaviours measured in the rCPT variable stimulus duration (vSD) and the variable intertrial interval (vITI) schedules.MethodsTwo cohorts of 36 female C57BL/6JRj mice were examined separately in the rCPT vSD and vITI schedules. Both cohorts received antagonists of the following adrenoceptors: α1 (doxazosin, DOX: 1.0, 3.0, 10.0 mg/kg), α2 (yohimbine, YOH: 0.1, 0.3, 1.0 mg/kg), and β1/2 (propranolol, PRO: 1.0, 3.0, 10.0 mg/kg) in consecutive balanced Latin square designs with flanking reference measurements. The antagonists were subsequently examined for effects on locomotor activity.ResultsDOX showed similar effects in both schedules, improving discriminability and accuracy, and reducing responding and impulsivity, and DOX also reduced locomotor activity. YOH showed prominent effects in the vSD schedule to increase responding and impulsivity, while impairing discriminability and accuracy. YOH did not affect locomotor activity. PRO increased responding and impulsivity, decreased accuracy, but did not affect discriminability or locomotor activity.ConclusionAntagonism of α2 or β1/2 adrenoceptors caused similar increases in responding and impulsivity and worsened attentional performance, while α1 adrenoceptor antagonism showed the opposite effects. Our results suggest that endogenous NA exerts bidirectional control of most behaviours in the rCPT. The parallel vSD and vITI studies showed a substantial overlap in effects, but also some differences that indicate differing sensitivity towards noradrenergic manipulations.

Topographical aspects of brief-stimulus presentations: A re-examination of the problem of conditioned reinforcement

Three pigeons were exposed to second-order schedules in which responding under a fixed-interval (FI) component schedule was reinforced according to a variable-interval (VI) schedule of food reinforcement. Completion of each component resulted in either (1) brief presentation of a stimulus present during reinforcement (paired brief stimulus), (2) brief presentation of a stimulus not present during reinforcement (nonpaired brief stimulus), or (3) no stimulus presentation (tandem schedule). Under the two nonpaired brief stimulus conditions, either a change in keylight color or onset of houselight illumination was used as the brief stimulus. Similar patterns of keypecking occurred under tandem and nonpaired keylight brief-stimulus presentations, whereas nonpaired houselight brief-stimulus presentations generated positively accelerated within-component keypeck patterning for two pigeons. When the same keylight brief stimulus was paired with food, positively accelerated patterns of keypecking were obtained for all pigeons. Differences in the effects of nonpaired brief-stimulus presentations on second-order schedule performance suggest that component schedule patterning under nonpaired brief-stimulus procedures is a function of the particular type of stimulus used (i.e., houselight versus keylight). These results suggest that (1) brief houselight illumination may function as a sensory reinforcer, and (2) a briefly presented food-paired stimulus can function as an effective conditioned reinforcer.

Choice dynamics in concurrent ratio schedules of reinforcement.

The generalized matching law predicts performance on concurrent schedules when variable-interval schedules are programmed but is trivially applicable when independent ratio schedules are used. Responding usually is exclusive to the schedule with the lowest response requirement. Determining a method to program concurrent ratio schedules such that matching analyses can be usefully employed would extend the generality of matching research and lead to new avenues of research. In the present experiments, ratio schedules were programmed dependently such that responses to either of the two options progressed the requirement on both schedules. Responding is not exclusive because the probability of reinforcement increases on both schedules as responses are allocated to either schedule. In Experiment 1, performance on concurrent variable-ratio schedules was assessed, and reinforcer ratios were varied across conditions to investigate changes in sensitivity. Additionally, the length of a changeover delay was manipulated. In Experiment 2, performance was compared under concurrently available, dependently programmed variable-ratio and fixed-ratio schedules. Performance was well described by the generalized matching law. Increases in the changeover delay decreased sensitivity, whereas sensitivity was higher when variable-ratio schedules were employed, compared with fixed-ratio schedules. Concurrent ratio schedules can be a viable approach to studying functional differences between ratio and interval schedules.

A test of the evolutionary theory's account of punishment superimposed on single-alternative schedules.

A test of the evolutionary theory was conducted by replicating Bradshaw et al.'s (1977, 1978, 1979) experiments in which human participants worked on single-alternative variable-interval (VI) schedules of reinforcement under three punishment conditions: no punishment, superimposed VI punishment, and superimposed variable-ratio (VR) punishment. Artificial organisms (AOs) animated by the theory worked in the same environments. Four principal findings were reported for the human participants: (1) their behavior was well described by an hyperbola in all conditions, (2) the asymptote of the hyperbola under VI punishment was equal to the asymptote in the absence of punishment, but the asymptote under VR punishment was lower than the asymptote in the absence of punishment, (3) the parameter in the denominator of the hyperbola was larger under both VI and VR punishment than in the absence of punishment, and (4) response suppression under punishment was greater at lower than at higher reinforcement frequencies. These four outcomes were also observed in the behavior of the AOs working in the same environments, thereby confirming the theory's first-order predictions about the effects of punishment on single-alternative responding.

Assessing the nature of premature responses in the rodent continuous performance test variable intertrial interval schedule using atomoxetine and amphetamine

BackgroundRodent operant tests that include premature responses (PR) as a measure of impulsivity commonly use variable intertrial interval (vITI) schedules. The rodent continuous performance test (rCPT) is suitable for a vITI schedule. New MethodWe optimised the analysis for a rCPT vITI schedule with intertrial intervals (ITIs) of 3, 6, and 12 s. Examining the nature of first (FiT) and following touches (FoT) to the blank screen led to a separate quantification of these two behaviours into the first touches level (%FiT) and the following-to-first touches ratio (FoT/FiT). ResultsFiTs occurred more frequently in the 12 s ITIs than at shorter ITIs. Within 12 s ITIs, %FiT was only moderately higher during the last half than the first half, suggesting that long ITIs have a minimal effect on impulsivity, but allow a longer time for its detection. %FiT and the FoT/FiT ratio were uncorrelated. %FiT was negatively correlated with response criterion (C) and uncorrelated with discriminability. Conversely, FoT/FiT ratio was negatively correlated with discriminability, without correlation to C. Atomoxetine decreased %FiT but did not affect FoT/FiT ratio. Amphetamine increased %FiT and decreased the FoT/FiT ratio. Comparison with Existing Method(s)The results suggest that %FiT is analogous to %PR in related tasks and is a more suitable measure of waiting impulsivity in the rCPT. FoT/FiT ratio is unrelated to %FiT. ConclusionsLong ITIs increase the detectability of, but has minimal effect on, waiting impulsivity. %FiT is analogous to %PR in related tasks, while the FoT/FiT ratio is a separate behaviour requiring further characterization.

Evaluating habit formation across pairs of female and male selectively bred alcohol-preferring and non-preferring rats

Some individuals with alcohol use disorder (AUD) continue to drink because they have developed a habit where they do not consider the consequences of their actions. Genetically selected lines of alcohol-preferring and non-preferring rats allow for exploration of how specific endophenotypes, such as tendency to form habits, may be risk factors that interact with a genetic predisposition of AUD. While high alcohol drinking (HAD) and alcohol-preferring (P) rats were selectively bred to consume high amounts of freely available ethanol, they exhibit differences in alcohol-seeking behaviors as well as impulsive behaviors, and may represent different behavioral models of AUD. The goal of the current study was to compare the tendency to develop habitual behaviors across female and male HAD1, HAD2, and P rats and their respective alcohol non-preferring counterparts. Alcohol-naïve rats were trained on a variable interval schedule using a non-ethanol reinforcer and were then tested in two extinction sessions, one prior to a reinforcer devaluation (conditioned taste aversion) procedure and one after. There were no differences in total lever presses between P and alcohol non-preferring (NP) rats, but there were differences between HAD and low-alcohol drinking (LAD) rats. All six strains decreased lever pressing after reinforcer devaluation. However, P and NP females did not increase latency to first lever press after devaluation, suggesting some inclination toward habitual behavior that was not apparent in either the HAD or LAD lines. Selective breeding for alcohol preference does not seem to influence the tendency to form habits, whereas background strain and sex may have an influence on this behavior.

Rate matching, probability matching, and optimization in concurrent ratio schedules.

Much research has documented rate matching in concurrent variable-interval schedules, but comparatively little research has examined performance in concurrent variable-ratio schedules, except in discrete-trials procedures that sometimes produce probability matching. One should expect that the two types of schedule would result in different performances, because ratio schedules cannot improve with time the way interval schedules do; ratio schedules lack the temporal dynamics of interval schedules. The present experiment exposed rats to concurrent variable-ratio schedules. Seven unsignaled components were presented in random order within each daily session, with probability ratios ranging from 1:8 to 8:1. Three conditions were studied that varied the overall probability of food while leaving probability ratios the same. Choice appeared to conform to probability matching, because sensitivities in the rate-matching relation were close to 0.5, whereas sensitivities to probability ratio were close to 1.0. The sensitivities alone, however, could not confirm probability matching, because undermatching to rate occurs often. Analyses at smaller time scales supported the interpretation of probability matching. In particular, control by food deliveries was highly local in concurrent variable-ratio schedules, in contrast with concurrent variable-interval schedules, in which control is extended. Activity continued to switch between alternatives throughout components, contradicting optimal sampling theory.

Machine learning with a snapshot of data: Spiking neural network 'predicts' reinforcement histories of pigeons' choice behavior.

An accumulated body of choice research has demonstrated that choice behavior can be understood within the context of its history of reinforcement by measuring response patterns. Traditionally, work on predicting choice behaviors has been based on the relationship between the history of reinforcement—the reinforcer arrangement used in training conditions—and choice behavior. We suggest an alternative method that treats the reinforcement history as unknown and focuses only on operant choices to accurately predict (more precisely, retrodict) reinforcement histories. We trained machine learning models known as artificial spiking neural networks (SNNs) on previously published pigeon datasets to detect patterns in choices with specific reinforcement histories—seven arranged concurrent variable‐interval schedules in effect for nine reinforcers. Notably, SNN extracted information from a small ‘window’ of observational data to predict reinforcer arrangements. The models' generalization ability was then tested with new choices of the same pigeons to predict the type of schedule used in training. We examined whether the amount of the data provided affected the prediction accuracy and our results demonstrated that choices made by the pigeons immediately after the delivery of reinforcers provided sufficient information for the model to determine the reinforcement history. These results support the idea that SNNs can process small sets of behavioral data for pattern detection, when the reinforcement history is unknown. This novel approach can influence our decisions to determine appropriate interventions; it can be a valuable addition to our toolbox, for both therapy design and research.

The effects of acamprosate on prefrontal cortical function are mimicked by CaCl2 and they are influenced by the history of alcohol exposure

Alcohol use disorder is associated with functional changes in the medial prefrontal cortex (mPFC), which include altered glutamatergic transmission and deficits in executive functions that contribute to relapse. Acamprosate (calcium-bis N-acetylhomotaurinate) reduces alcohol craving and relapse, effects that are thought to be mediated by acamprosate's ability to ameliorate alcohol-induced dysregulation of glutamatergic signaling. Treatment with acamprosate and its active moiety calcium (CaCl2) both improve deficits in cognitive flexibility in postdependent mice following chronic intermittent ethanol (CIE) exposure. Here, we show that mice that self-administered alcohol under goal-directed conditions (i.e., operant responding on a fixed-ratio schedule) also display similar deficits in cognitive flexibility and altered glutamatergic signaling in the mPFC, both of which were improved with acamprosate or CaCl2. However, under conditions shown to bias behavior towards habitual responding (operant self-administration after CIE exposure, or on a variable interval schedule), alcohol-induced changes to glutamatergic transmission were unaffected by either acamprosate or CaCl2 treatment. Together, these findings suggest that the variable effects of acamprosate on synaptic signaling may reflect a shift in mPFC networks related to the loss of behavioral control in habitual alcohol-seeking.

Analysis of variability of pigeons’ pecking location under variable-interval schedules

Previous studies have examined the variability induced by reinforcement schedules. These studies have suggested that the reinforcement rate and periodicity of reinforcement are factors that determine the degree of variability. The present study aimed to examine the effect of the above factors on variability in a variable-interval schedule. We measured the variability in the location of pigeon pecking responses for a single variable-interval schedule under a wide range of reinforcement rates. A circular response area of 22.4 cm in diameter was used so that the pecking responses were effective over a wide range. There was no systematic relationship between reinforcement rate and variability. In addition, consistent temporal change of the location variability was not shown in the variable-interval schedule. The results of the present study and previous studies would be accounted for by the suggestion that the periodicity of reinforcement or temporal discrimination affects the variability. In addition, the present study suggests that a molecular analysis is needed to examine the effect of the reinforcement schedule on variability.

Behavioral ephemera, difficult discriminations, and behavioral stability.

Every species possesses abilities for successfully interacting with its environment. These result from phylogeny. In the laboratory, one may arrange artificial conditions that thwart an organism's abilities. The result may be a "phenomenon." With sufficient training, however, the phenomenon may prove to be ephemeral, as the organism's basic abilities reassert themselves. Pigeons respond extremely well to differences and nondifferences in rate of obtaining food. This ability may be thwarted in a variety of ways, but the results tend to be ephemeral. An example is an experiment that pitted pigeons' preference for unimpeded responding against their ability to respond to food rate. In a concurrent-chains procedure, the terminal links were identical variable-interval schedules, but in one terminal link, every response produced a timeout. The duration of the timeout varied, and preference varied with it, but the relation vanished with training, in keeping with the equality of food rate across the 2 terminal links. Some other examples of "phenomena" that tend to disappear with sufficient training and sufficient variation in experimental parameters are behavioral contrast, conditioned reinforcement, resistance to extinction, and suboptimal choice. These "phenomena" depend on pigeons' failing to make difficult discriminations. They appear to be behavioral ephemera.

Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants.

More effective treatments to reduce pathological alcohol drinking are needed. The glutamatergic system and the NMDA receptor (NMDAR), in particular, are implicated in behavioral and molecular consequences of chronic alcohol use, making the NMDAR a promising target for novel pharmacotherapeutics. Ethanol exposure upregulates Fyn, a protein tyrosine kinase that indirectly modulates NMDAR signaling by phosphorylating the NR2B subunit. The Src/Fyn kinase inhibitor saracatinib (AZD0530) reduces ethanol self-administration and enhances extinction of goal-directed ethanol-seeking in mice. However, less is known regarding how saracatinib affects habitual ethanol-seeking. Moreover, no prior studies have assessed the effects of Src/Fyn kinase inhibitors on alcohol-seeking or consumption in human participants. Here, we tested the effects of saracatinib on alcohol consumption and craving/seeking in two species, including the first trial of an Src/Fyn kinase inhibitor to reduce drinking in humans. Eighteen male C57BL/6NCrl mice underwent operant conditioning on a variable interval schedule to induce habitual responding for 10% ethanol/0.1% saccharin. Next, mice received 5 mg/kg saracatinib or vehicle 2 h or 30 min prior to contingency degradation to measure habitual responding. In the human study, 50 non-treatment seeking human participants who drank heavily and met DSM-IV criteria for alcohol abuse or dependence were randomized to receive 125 mg/day saracatinib (n = 33) or placebo (n = 17). Alcohol Drinking Paradigms (ADP) were completed in a controlled research setting: before and after 7–8 days of treatment. Each ADP involved consumption of a priming drink of alcohol (0.03 mg%) followed by ad libitum access (3 h) to 12 additional drinks (0.015 g%); the number of drinks consumed and craving (Alcohol Urge Questionnaire) were recorded. In mice, saracatinib did not affect habitual ethanol seeking or consumption at either time point. In human participants, no significant effects of saracatinib on alcohol craving or consumption were identified. These results in mice and humans suggest that Fyn kinase inhibition using saracatinib, at the doses tested here, may not reduce alcohol consumption or craving/seeking among those habitually consuming alcohol, in contrast to reports of positive effects of saracatinib in individuals that seek ethanol in a goal-directed manner. Nevertheless, future studies should confirm these negative findings using additional doses and schedules of saracatinib administration.