Interresponse Time Distributions Research Articles

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.

Effects of the dopamine depleting agent tetrabenazine on detailed temporal parameters of effort-related choice responding.

The dopamine-depleting agent tetrabenazine alters effort-based choice, suppressing food-reinforced behaviors with high response requirements, while increasing selection of low-cost options. In the present experiments, rats were tested on a concurrent fixed ratio 5/chow feeding choice task, in which high-carbohydrate Bio-serv pellets reinforced lever pressing and lab chow was concurrently available. Detailed timing of lever pressing was monitored with an event recording system, and the temporal characteristics of operant behavior seen after 1.0 mg/kg tetrabenazine or vehicle injections were analyzed. Tetrabenazine shifted choice, decreasing lever pressing but increasing chow intake. There was a small effect on the interresponse-time distribution within ratios, but marked increases in the total duration of pauses in responding. The postreinforcement-pause (PRP) distribution was bimodal, but tetrabenazine did not increase the duration of PRPs. Tetrabenazine increased time feeding and duration and number of feeding bouts, but did not affect feeding rate or total time spent lever pressing for pellets and consuming chow. Thus, TBZ appears to predominantly affect the relative allocation of lever pressing versus chow, with little alteration in consummatory motor acts involved in chow intake. Tetrabenazine is used to model motivational symptoms in psychopathology, and these effects in rats could have implications for psychiatric research.

Extending the Specificity of DRL 72-s Behavior for Screening Antidepressant-Like Effects of Glutamatergic Clinically Validated Anxiolytic or Antidepressant Drugs in Rats.

Both an agonist and its associated prodrug for metabotropic glutamate2/3 (mGlu2/3) receptors demonstrated anxiolytic efficacy in large, randomized, multicenter, double-blind, placebo-controlled trials studying patients with generalized anxiety disorder (GAD). These mGlu2/3 receptor agonists produced robust preclinical anxiolytic-like effects in rodent models. Several different metabotropic glutamate2 receptor positive allosteric modulators have been found to produce antidepressant-like effects on several preclinical screening paradigms, including differential-reinforcement-of-low-rate 72-second (DRL 72-s) behavior [increased reinforcers, decreased response rate, and cohesive rightward shifts in inter-response time distributions]. Although mGlu2/3 receptor agonists have not been tested formally for therapeutic effects in treating patients with major depressive disorder, these compounds generally fail to exert antidepressant-like effects in preclinical screening paradigms and did not improve depressive symptoms in GAD trials. Thus, the present studies were designed to test the potential antidepressant-like effects of the mGlu2/3 receptor agonist 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-bicarboxylate monohydrate (LY354740) on the DRL 72-s schedule. LY354740 did not test similarly to clinically validated antidepressant drugs when administered alone or when coadministered with the selective serotonin reuptake inhibitor fluoxetine in rats. Another glutamate-based antidepressant drug, the uncompetitive N-methyl-D-aspartate channel blocker racemic ketamine, exerted antidepressant-like effects when administered at subanesthetic doses in rats. The findings further support the specificity of rat DRL 72-s behavior when screening for anxiolytic versus antidepressant drugs and extend testing of compounds with glutamatergic mechanisms of action. SIGNIFICANCE STATEMENT: The metabotropic glutamate2/3 receptor agonist and clinically validated anxiolytic drug 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-bicarboxylate monohydrate did not test similar to antidepressant drugs (increased reinforcers, decreased response rate, and cohesive rightward shifts in the inter-response time distribution) when tested on differential-reinforcement-of-low-rate 72-second (DRL 72-s) behavior and also did not enhance the antidepressant-like effects of the serotonin reuptake inhibitor fluoxetine. The uncompetitive N-methyl-D-aspartate receptor antagonist ketamine increased the reinforcement rate, decreased the response rate, and induced a rightward shift in the inter-response time distribution similar to antidepressant drugs; these results confirm the utility of DRL 72-s schedule of reinforcement when testing clinically validated anxiolytic versus antidepressant glutamatergic drugs.

Task-Dependent Differences in Operant Behaviors of Rats With Acute Exposure to High Ambient Temperature: A Potential Role of Hippocampal Dopamine Reuptake Transporters.

Behavioral or cognitive functions are known to be influenced by thermal stress from the change in ambient temperature (Ta). However, little is known about how increased Ta (i.e., when the weather becomes warm or hot) may affect operant conditioned behavior and the neural substrates involved. The present study thus investigated the effects of high Ta on operant behaviors maintained on a fixed-ratio 1 (FR1) and a differential reinforcement for low-rate responding 10 s (DRL 10-s) schedule of reinforcement. The rats were randomly assigned to three groups receiving acute exposure to Ta of 23°C, 28°C, and 35°C, respectively, for evaluating the effects of high Ta exposure on four behavioral tests. Behavioral responses in an elevated T-maze and locomotor activity were not affected by Ta treatment. Regarding operant tests, while the total responses of FR1 behavior were decreased only under 35°C when compared with the control group of 23°C, those of DRL 10-s behavior were significantly reduced in both groups of 28°C and 35°C. Distinct patterns of inter-response time (IRT) distribution of DRL behavior appeared among the three groups; between-group differences of behavioral changes produced by high Ta exposure were confirmed by quantitative analyses of IRT data. Western blot assays of dopamine (DA) D1 and D2 receptor, DA transporter (DAT) and brain-derived neurotrophic factor (BDNF) were conducted for the sample tissues collected in six brain areas from all the subjects after acute high Ta exposure. Significant Ta-related effects were only revealed in the dorsal hippocampus (dHIP). In which, the DAT levels were increased in a Ta-dependent fashion that was associated with operant behavior changes under high Ta exposure. And, there as an increased level of D1 receptors in the 28°C group. In summary, these data indicate that the performance of operant behavior affected by the present high Ta exposure is task-dependent, and these changes of operant behaviors cannot be attributed to gross motor function or anxiety being affected. The regulation of dHIP DAT may be involved in this operant behavioral change under high Ta exposure.

The natural mathematics of behavior analysis.

Models that generate event records have very general scope regarding the dimensions of the target behavior that we measure. From a set of predicted event records, we can generate predictions for any dependent variable that we could compute from the event records of our subjects. In this sense, models that generate event records permit us a freely multivariate analysis. To explore this proposition, we conducted a multivariate examination of Catania's Operant Reserve on single VI schedules in transition using a Markov Chain Monte Carlo scheme for Approximate Bayesian Computation. Although we found systematic deviations between our implementation of Catania's Operant Reserve and our observed data (e.g., mismatches in the shape of the interresponse time distributions), the general approach that we have demonstrated represents an avenue for modelling behavior that transcends the typical constraints of algebraic models.

About bouts: A heterogeneous tandem schedule of reinforcement reveals dissociable components of operant behavior in Fischer rats.

According to the biexponential refractory model (BERM) of variable-interval (VI) performance, operant behavior is organized in bouts, described by 3 dissociable components: between-bout interresponse times (IRTs), within-bout IRTs, and bout lengths. Research has shown that between-bout IRTs are sensitive to changes in rate of reinforcement and reinforcer efficacy, the length of some bouts is selectively sensitive to changes in response-reinforcer contingencies, and within-bout IRTs are relatively insensitive to both manipulations. BERM assumes that within- and between-bout IRTs are exponentially distributed, and bout lengths are described by a mixture of negative binomial and geometric distributions. To assess BERM assumptions and the interpretation of associated findings, Fischer 344/DuCrl rats were trained on a heterogeneous tandem VI fixed-ratio (FR) schedule of reinforcement intended to dissociate the components of operant behavior. Initial (VI) and terminal (FR) links were programmed on separate levers; no stimulus signaled the completion of the initial link. FR requirement, VI requirement, and deprivation level were varied. Typical performance consisted of single responses on the VI lever separated by response runs on the FR lever. It was hypothesized that (a) the interval between the end of each FR run and the first subsequent VI response (FR-VI IRTs) would constitute between-bout IRTs, and would be sensitive to changes in VI requirement and deprivation level, (b) FR runs would constitute response bouts, so the length of a fraction of them would be selectively sensitive to changes in FR requirement, and (c) intervals between consecutive FR responses (FR-FR IRTs) would constitute within-bout IRTs, and would be relatively robust to all manipulations. Findings were consistent with these expectations. The underlying distributions of FR-FR IRTs, FR-VI IRTs, and FR run lengths, however, were inconsistent with BERM assumptions. These data support the distinct components of operant performance, but challenge the simple processes assumed to underlie their generation. (PsycINFO Database Record

Response-bout analysis of interresponse times in variable-ratio and variable-interval schedules

The purpose of this study was to analyze the response pattern difference between variable-ratio (VR) and variable-interval (VI) schedules of reinforcement by modeling interresponse time distributions of rats’ lever presses. All eight rats showed higher response rates under VR 30 than under inter-reinforcement intervals yoked VI. The 30 models consisting of single Exponential (with and without the lower limit on interresponse times), Weibull, Normal, Log-Normal or Gamma distributions, all possible two component combinations of those, and 3 and 4 component models consisting of Weibull, Normal, Log-Normal, or Gamma distribution combinations were compared. The 4 component Log-Normal model was the best in terms of the Akaike information criterion and visual inspection of fitting outcome. Parameter estimates for the L4 model showed that the VR-VI response rate difference is due to a difference in short interresponse times or within bout responses. This results suggests that the VR-VI response rate difference is not an indication of a difference in the overall tendency to respond but it is rather a difference in terms of what types of response patterns are engendered between the two schedules.

Interval timing under a behavioral microscope: Dissociating motivational and timing processes in fixed-interval performance.

The distribution of latencies and interresponse times (IRTs) of rats was compared between two fixed-interval (FI) schedules of food reinforcement (FI 30s and FI 90s), and between two levels of food deprivation. Computational modeling revealed that latencies and IRTs were well described by mixture probability distributions embodying two-state Markov chains. Analysis of these models revealed that only a subset of latencies is sensitive to the periodicity of reinforcement, and prefeeding only reduces the size of this subset. The distribution of IRTs suggests that behavior in FI schedules is organized in bouts that lengthen and ramp up in frequency with proximity to reinforcement. Prefeeding slowed down the lengthening of bouts and increased the time between bouts. When concatenated, latency and IRT models adequately reproduced sigmoidal FI response functions. These findings suggest that behavior in FI schedules fluctuates in and out of schedule control; an account of such fluctuation suggests that timing and motivation are dissociable components of FI performance. These mixture-distribution models also provide novel insights on the motivational, associative, and timing processes expressed in FI performance. These processes may be obscured, however, when performance in timing tasks is analyzed in terms of mean response rates.

Effects of Intranasal Oxytocin on Aggressive Responding in Antisocial Personality Disorder

The oxytocin receptor is important in several domains of social behavior, and administration of oxytocin modulates social responding in several mammalian species, including humans. Oxytocin has both therapeutic and scientific potential for elucidating the neural and behavioral mechanisms governing social behavior. In the present study, operationally-defined aggressive behavior of six males with Antisocial Personality Disorder (ASPD) was measured following acute intranasal oxytocin dosing (12, 24, and 48 international units) and placebo, using a well-validated laboratory task of human aggression (Point-Subtraction Aggression Paradigm, or PSAP). The PSAP provides participants with concurrently available monetary-earning and operationally-defined aggressive response options, maintained by fixed ratio schedules of consequences. Shifts in response rates and inter-response time (IRT) distributions were observed on the aggressive response option following oxytocin doses, relative to placebo. Few changes were observed in monetary-reinforced responding. However, across participants the direction and magnitude of changes in aggressive responding were not systematically related to dose. No trends were observed between psychometric or physiological data and oxytocin dosing or aggressive behavior. While this report is to our knowledge the first to examine the acute effects of oxytocin in this population at high risk for violence and other forms of antisocial behavior, several limitations in the experimental design and the results cast the study as a preliminary report. Strategies for more extensive future projects are discussed.

Ketamine, but not MK-801, produces antidepressant-like effects in rats responding on a differential-reinforcement-of-low-rate operant schedule

The noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been shown to produce rapid and lasting antidepressant effects in treatment-resistant patients with major depressive disorder and in preclinical behavioral assays. The present study sought to extend the preclinical antidepressant-like effects of ketamine using the differential-reinforcement-of-low-rate 72 s operant task in rats, as well as to determine whether the more selective and higher affinity NMDA receptor antagonist MK-801 produced antidepressant-like effects similar to those of ketamine. Ketamine, the NMDA receptor agonist N-methyl-D-aspartic acid, the tricyclic antidepressant imipramine, and the selective serotonin reuptake inhibitor fluoxetine all produced antidepressant-like effects by increasing the number of reinforcers, decreasing the number of responses, and producing a rightward shift in the peak location of the inter-response time distributions. Conversely, MK-801 and the dopamine receptor agonist D-amphetamine produced a psychostimulant-like effect by decreasing the number of reinforcers, increasing the number of responses, and producing a leftward shift in the peak location of the inter-response time distributions. Although a subeffective dose of ketamine attenuated the antidepressant-like effects of NMDA, a subeffective dose of NMDA did not alter the antidepressant-like effects of ketamine. These data indicate that ketamine and MK-801 produced dissociable effects in the differential-reinforcement-of-low-rate 72 s task, and further suggest that the underlying mechanisms responsible for the antidepressant effects of ketamine may be unique to ketamine and not shared by all NMDA receptor antagonists.

An affordance analysis of unconditioned lever pressing in rats and hamsters

Two experiments were conducted to assess the effect of lever height on lever pressing that was not explicitly reinforced – i.e., operant-level responding. Two rodent species were used as subjects, rats (Experiment 1) and hamsters (Experiment 2), aiming to compare the behavioral support offered by one lever at various heights relative to the subjects’ body size. Results showed that lever height had a substantial effect on response rate. The rate of lever pressing varied similarly for rats and hamsters as a function of lever height, when lever height was re-scaled relative to body size. The distribution of inter-response times showed that lever pressing was organized in bouts separated by pauses. This pattern of responding was accurately described in both experiments by a mixture of two exponential distributions. These findings support an analysis of affordances in non-human species.

Activation of Adenosine1 Receptors Induces Antidepressant-Like, Anti-Impulsive Effects on Differential Reinforcement of Low-Rate 72-s Behavior in Rats

Stress and psychiatric illness have been associated with a dysregulation of glutamatergic neurotransmission. Recently, positive allosteric modulators (PAMs) of the metabotropic glutamate 2 (mGlu₂) receptor have been found to exert antidepressant-like activity in rats performing under a differential reinforcement of low rate (DRL) 72-s schedule. An autoreceptor role at glutamatergic synapses is the most salient physiological role played by the mGlu₂ receptor. Adenosine A₁ receptors play a heteroreceptor role at many of the same forebrain synapses where mGlu₂ autoreceptors are found. Agonists and/or PAMs of mGlu₂ receptors act similarly to adenosine A₁ receptor agonists with respect to a wide range of electrophysiological, biochemical, and behavioral responses mediated by limbic circuitry thought to play a role in the pathophysiology of neuropsychiatric disease and to mediate therapeutic drug effects. Therefore, the role of adenosine A₁ receptor activation on rat DRL 72-s behavior was explored to provide preclinical evidence consistent or inconsistent with potential antidepressant effects. The adenosine A₁ receptor agonist N⁶-cyclohexyladenosine (CHA) increased the reinforcement rate, decreased the response rate, and induced a rightward shift in inter-response time distributions in a dose-dependent fashion similar to most known antidepressant drugs. The adenosine A₁ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) blocked these antidepressant-like effects. These novel observations with CHA and DPCPX suggest that activation of adenosine A₁ receptors could contribute to antidepressant effects, in addition to previous preclinical reports of anxiolytic and antipsychotic effects. By implication, targeting a dysregulated glutamatergic system may be an important principle in discovering novel antidepressant agents that may also possess anti-impulsive activity.

THE ISOLATION OF MOTIVATIONAL, MOTORIC, AND SCHEDULE EFFECTS ON OPERANT PERFORMANCE: A MODELING APPROACH

Dissociating motoric and motivational effects of pharmacological manipulations on operant behavior is a substantial challenge. To address this problem, we applied a response-bout analysis to data from rats trained to lever press for sucrose on variable-interval (VI) schedules of reinforcement. Motoric, motivational, and schedule factors (effort requirement, deprivation level, and schedule requirements, respectively) were manipulated. Bout analysis found that interresponse times (IRTs) were described by a mixture of two exponential distributions, one characterizing IRTs within response bouts, another characterizing intervals between bouts. Increasing effort requirement lengthened the shortest IRT (the refractory period between responses). Adding a ratio requirement increased the length and density of response bouts. Both manipulations also decreased the bout-initiation rate. In contrast, food deprivation only increased the bout-initiation rate. Changes in the distribution of IRTs over time showed that responses during extinction were also emitted in bouts, and that the decrease in response rate was primarily due to progressively longer intervals between bouts. Taken together, these results suggest that changes in the refractory period indicate motoric effects, whereas selective alterations in bout initiation rate indicate incentive-motivational effects. These findings support the use of response-bout analyses to identify the influence of pharmacological manipulations on processes underlying operant performance.

EDITORIAL: TRANSLATIONAL RESEARCH IN JEAB

Psychology students are taught about the differences between basic and applied research. A popular research methods textbook, for instance, states that “the major goal of basic research is to acquire general information about a phenomenon, with little emphasis placed on applications to real-world examples of the phenomenon” (Bordens & Abbott, 2002, p. 19). Another text asserts that basic research “establishes a reservoir of data, theoretical explanations, and concepts that can be tapped by the applied researcher” (Kantowitz, Roediger, & Elmes, 1997, p. 17). Ideally, of course, students are taught that there is not always a clear boundary between basic and applied research, and that many psychological studies have characteristics of both. For instance, a study may examine the applicability of a behavioral principle or theory in a clinical population, and this research can be of real value to both basic and applied researchers. A good study of this type can assist applied researchers in developing more effective treatment procedures, while at the same time it can give basic researchers information about a behavioral principle's generality, its limitations, and possibly about ways to refine, extend, or improve it. JEAB is known mainly for publishing basic research on the behavior of individual organisms. Yet from its beginnings, this journal has published occasional articles that bridge the gap between basic and applied research. In its first few years, JEAB published reports on the operant control of stuttering (Flanagan, Goldiamond, & Azrin, 1958), on the behavior of psychiatric patients under basic reinforcement schedules (e.g., Ayllon & Azrin, 1964; Ayllon & Haughton, 1962; Hutchinson & Azrin, 1961), and on “The psychiatric nurse as a behavioral engineer” (Ayllon & Michael, 1959). In later years, there have been articles on teaching impulsive children to tolerate delays (Schweitzer & Sulzer-Azaroff, 1988), on the development of equivalence relations between visual stimuli and drugs (DeGrandpre, Bickel, & Higgins, 1992), on the transfer of arousal functions in spider-fearful individuals (Smyth, Barnes-Holmes, & Forsyth, 2006), and on how a summed-exponential model of interresponse time distributions can be used to analyze the durations of wars (Nevin, 2008). These are just a few examples of JEAB articles that have demonstrated the application of basic behavioral principles beyond the operant laboratory. This special issue on translational research, therefore, does not venture into completely new territory for JEAB, although it does reflect a recent trend in the behavioral sciences toward increased interest in research that extends basic principles of behavior beyond the laboratory. It seems very fitting that JEAB, as one of the primary journals that publishes original research on basic behavioral principles, should continue to feature research that demonstrates the extension of these principles to nonlaboratory situations. This special issue has two main purposes. The first is to showcase some of the excellent translational work that is currently being conducted in many different areas. The articles in this issue cover a wide assortment of topics and behavioral principles, ranging from an application of the matching law to the speech patterns of delinquent boys to an fMRI study on risk perception in pathological gamblers. There are indeed many different areas in which modern behavioral principles and concepts can be fruitfully applied. The second purpose of this special issue is to communicate our intention to publish more high-quality translational research as a regular part of future issues of JEAB. As an important step toward achieving this goal, I am pleased to announce that F. Charles (Bud) Mace has accepted the position of JEAB's first Editor for Translational Research. Researchers who conduct translational research are invited and encouraged to submit their manuscripts to this journal. Bud's extensive experience in the area of translational research will ensure that manuscripts on translational research receive competent and appropriate evaluation and feedback. This special issue, and our plans to include more translational research in the future issues, therefore represent the continuation of a long tradition for JEAB. In the five decades of JEAB's existence, basic research has produced a wealth of new knowledge about the behavior of individual organisms. The recent growth in the quantity and variety of translational research is a sign that the time is right for tapping into this reservoir of data, theoretical explanations, and concepts, and demonstrating their importance outside the laboratory.

Antidepressant-like or anxiolytic-like actions of topiramate alone or co-administered with intra-lateral septal infusions of neuropeptide Y in male Wistar rats

We tested the effects of intra-lateral septal infusions of neuropeptide Y (NPY) combined with systemic injections of topiramate in the DRL-72 s paradigm and the elevated plus-maze test in male Wistar rats. Intra-lateral septal infusions of desipramine (5.0 μg/μl; P < 0.05) or intra-lateral septal infusions of NPY (3.0 μg/μl, P < 0.05; 3.5 μg/μl, P < 0.05) or systemic injections of topiramate (20.0 mg/kg, P < 0.05; 30.0 mg/kg, P < 0.05) or subthreshold doses of topiramate (10.0 mg/kg) combined with intra-lateral septal infusions of subthreshold doses of NPY (2.5 μg/μl; P < 0.05) induced a dose-dependent increase in reinforced lever presses and a cohesive rightward shift of the inter-response time distribution in the DRL 72 s task. In the elevated plus-maze test, intra-lateral septal infusions of NPY (3.0 μg/μl, P < 0.05; 3.5 μg/μl, P < 0.05) or midazolam (10.0 μg/μl; P < 0.05) or systemic injections of topiramate (20.0 mg/kg, P < 0.05; 30.0 mg/kg, P < 0.05) or subthreshold doses of systemic injections of topiramate (10.0 mg/kg) combined with intra-lateral septal infusions of subthreshold doses of NPY (2.5 μg/μl; P < 0.05) increased the exploration of the open arms without affecting locomotion. In conclusion, intra-septal NPY has anxiolytic effects in the EPM, and antidepressant effects in the DRL 72 s test. Similarly, systemic topiramate has anxiolytic effects in the EPM, and antidepressant effects in the DRL 72 s test. Finally, a combination of subthreshold doses of NPY and topiramate together also have anxiolytic and antidepressant effects, suggesting a synergistic effect.

The triple reuptake inhibitor DOV216,303 exhibits limited antidepressant-like properties in the differential reinforcement of low-rate 72-second responding assay, likely due to dopamine reuptake inhibition

There is a need for antidepressants with novel mechanisms of action. One approach has been to develop compounds that inhibit reuptake of all three monoamines in the central nervous system, for example DOV216,303. Differential reinforcement of low-rate (72-s) responding is a behavioral test that is predictive of antidepressant-like properties. The effects of antidepressant compounds belonging to multiple classes, the anxiolytic diazepam and the antipsychotic haloperidol, were assessed in the DRL-72s task. Subsequently, the antidepressant-like properties of acute DOV216,303 were assessed. The selective serotonin reuptake inhibitor fluvoxamine, the preferential norepinephrine reuptake inhibitor desipramine and the tricyclic antidepressant imipramine exhibited antidepressant-like properties in the DRL-72s task. The atypical antidepressant bupropion, which inhibits dopamine and norepinephrine reuptake, and the selective dopamine transporter inhibitor GBR12909, changed reinforcement and response rates and inter-response time distribution in an opposite direction compared with the antidepressant compounds tested. The antipsychotic haloperidol exhibited antidepressant-like properties by increasing reinforcement rate, but failed to alter inter-response time distribution. Diazepam did not change reinforcement or response rates or inter-response time distribution. The triple reuptake inhibitor DOV216,303 significantly enhanced reinforcement rate at one intermediate dose, but exhibited similar effects as bupropion and GBR12909 on inter-response time distribution. The studies identified limited antidepressant-like properties of the triple reuptake inhibitor DOV216,303, likely due to dopamine transporter inhibition counteracting the effects of norepinephrine and serotonin transporter inhibition.

Differential involvement of prefrontal cortex, striatum, and hippocampus in DRL performance in mice

Behavioral effects of neurotoxic lesions of the hippocampus, medial prefrontal (prelimbic, infralimbic and anterior cingulate) cortex or dorsal striatum were assessed using a DRL-10s schedule in mice. Post-operative acquisition data indicate that mice with hippocampal, but not prefrontal or striatal lesions received fewer reinforcements during daily 30-min sessions, and were less efficient in the timing of their responses. Additional analysis of inter-response-time (IRT) distributions revealed that the responses of hippocampal-lesioned mice exhibited undistinguishable responses for short IRTs (up to 9s). In addition, prefrontal-lesioned mice demonstrated a degradation of performance with further testing, and a flattened IRT distribution at late test phase, while striatal-lesioned mice behaved similarly to sham-lesioned mice. These results are interpreted in terms of known functions of the hippocampus in behavioral inhibition, and of the prefrontal cortex in executive control/decision making (and time production).

AGGRESSION AS POSITIVE REINFORCEMENT IN MICE UNDER VARIOUS RATIO‐ AND TIME‐BASED REINFORCEMENT SCHEDULES

There is evidence suggesting aggression may be a positive reinforcer in many species. However, only a few studies have examined the characteristics of aggression as a positive reinforcer in mice. Four types of reinforcement schedules were examined in the current experiment using male Swiss CFW albino mice in a resident-intruder model of aggression as a positive reinforcer. A nose poke response on an operant conditioning panel was reinforced under fixed-ratio (FR 8), fixed-interval (FI 5-min), progressive ratio (PR 2), or differential reinforcement of low rate behavior reinforcement schedules (DRL 40-s and DRL 80-s). In the FR conditions, nose pokes were maintained by aggression and extinguished when the aggression contingency was removed. There were long postreinforcement pauses followed by bursts of responses with short interresponse times (IRTs). In the FI conditions, nose pokes were maintained by aggression, occurred more frequently as the interval elapsed, and extinguished when the contingency was removed. In the PR conditions, nose pokes were maintained by aggression, postreinforcement pauses increased as the ratio requirement increased, and responding was extinguished when the aggression contingency was removed. In the DRL conditions, the nose poke rate decreased, while the proportional distributions of IRTs and postreinforcement pauses shifted toward longer durations as the DRL interval increased. However, most responses occurred before the minimum IRT interval elapsed, suggesting weak temporal control of behavior. Overall, the findings suggest aggression can be a positive reinforcer for nose poke responses in mice on ratio- and time-based reinforcement schedules.

Beyond continuous mathematics and traditional scientific analysis: Understanding and mining Wolfram's A New Kind of Science

In A New Kind of Science, Stephen Wolfram recommends abandoning traditional scientific analysis and the continuous mathematical description that it affords in favor of the study of simple rules. He focuses on a machine known as a cellular automaton as the prototype generator of complex phenomena such as those we see in nature. The simplest cellular automaton consists of a row of cells, each existing in one of two states. The states of the cells are updated from moment to moment by simple rules. Wolfram shows that these machines and their many variations can generate a host of outcomes ranging from very simple to extremely complex. He argues that among these outcomes representations of all the phenomena in the universe will be found, including presumably the behavior of organisms. The output of cellular automata can be mapped to behavior by considering, for example, one of the states of a cell to represent the emission of a behavior. For some cellular automaton rules, these mappings generate cumulative records and inter-response time distributions that are similar to those produced by live organisms. In addition, at least one cellular automaton generates the Herrnstein hyperbola as an emergent outcome. These results suggest that Wolfram's program and its mainstream version, which is known as complexity theory, is worth pursuing as a possible means of understanding and accounting for the behavior of organisms.

Timing and space usage are disrupted by amphetamine in rats maintained on DRL 24-s and DRL 72-s schedules of reinforcement

A differential-reinforcement-of-low-rate schedule (DRL) delivers reinforcement only when the interresponse time (IRT) exceeds a fixed time interval, thereby shaping rats to discriminate the timing of their responses. However, little is known about the motor behavior and location of the rats in the chamber during the IRTs that lead to reinforcement. Although amphetamine is known to disrupt DRL timing behavior, the effects of this drug on non-operant motor behavior during DRL performance has not yet been quantified. The purpose of this research was to measure the motor behavior (movement trajectories in the horizontal plane and spatial location in the plane) during longer IRTs after either vehicle or amphetamine treatment. Experimental chambers were constructed with a force-plate actometer as the floor, and while performing the operant task, the rats' motor behaviors were measured continuously with high temporal and spatial resolution. Separate groups of eight male Sprague-Dawley rats were maintained on either DRL 24-s or DRL 72-s schedules of water reinforcement in 4-h recording sessions. Analyses of IRT distributions showed that the rats' timing behavior conformed to their respective DRL requirements. In the absence of drug, analysis of motor behavior in pre-reinforcement intervals showed that rats located themselves away from the operandum and exhibited very low levels of movement. Rats exhibited a significant temporal diminution of horizontal movement that reached a minimum 4-8 s before the rats moved to the operandum to execute operant responses. Amphetamine treatment increased locomotion, abolished the temporal movement gradient, and brought the rats closer to the operandum compared to vehicle treatment. Movement changes induced by amphetamine were accompanied by degraded timing behavior. Taken together, the data show that DRL training induced rats to locate themselves away from the operandum and to remain nearly motionless during longer IRTs and that amphetamine treatment interfered with this complex of behavioral features.