This or not that: select and reject control of relational responding in rats using a blank comparison procedure with odor stimuli.

The blank comparison (BLC) task was developed to assess stimulus relations in discrimination learning; that is, are subjects learning to "select" the correct stimulus (S+) or "reject" the incorrect stimulus (S-) or both? This task has been used to study exclusion learning, mostly in humans and monkeys, and the present study extends the procedure to rats. The BLC task uses an ambiguous stimulus (BLC+/-) that replaces S+ (in the presence of S-) and replaces S- (in the presence of S+). In the current experiment, four rats were trained to remove session-novel scented lids from sand-filled cups in a two-choice, simultaneous presentation procedure called the Odor Span Task (OST) before being trained on the BLC procedure using odors as the discriminative stimuli. The BLC training procedure utilized simple discrimination training (S+ and S-) and added select (S+ and BLC-) and reject (BLC+ and S-) trial types. All rats demonstrated accurate performance in sessions with both select and reject type trials. Next, BLC probe trials were interspersed in standard OST sessions to assess the form of stimulus control in the OST. Rats performed accurately on select type probe trials (similar to baseline OST performance) and also showed above chance accuracy on reject type trials. Thus, we demonstrated that rats could acquire an odor-based version of the BLC task and that both select and exclusion-based (reject) relations were active in the OST. The finding of exclusion in rats under the rigorous BLC task conditions confirms that exclusion-based responding is not limited to humans and non-human primates.

Generalized, cross-modal, and incrementing non-matching-to-sample in rats.

Same/different concept learning has been demonstrated in previous research in rats using matching- and non-matching-to-sample procedures with olfactory stimuli. In Experiment 1, rats were trained on the non-matching-to-sample procedure with either three-dimensional (3D plastic objects; n = 3) or olfactory (household spices, n = 5) stimuli, then tested for transfer to novel stimuli of the same, and then the alternate, modality. While all three rats trained with olfactory stimuli showed generalized non-matching to novel odors, only one rat learned the 3D relation and showed generalized transfer to novel objects. Importantly, in this rat the 3D non-matching relation then immediately transferred to odors. In contrast, rats trained with scents did not show transfer to novel 3D stimuli until after training with one or two 3D stimulus sets. In Experiment 2, four rats were trained on an incrementing non-matching-to-sample task featuring 3D plastic objects as stimuli (3D Span Task). Responses to session-novel stimuli resulted in reinforcement. Only two rats learned the 3D Span Task; one rat performed with high accuracy even with up to 17 session-novel objects in a session. While these findings emphasize the exceptional olfactory discrimination of rats relative to that with 3D/tactile/visual cues, they also show that relational learning can be demonstrated in another modality in this species. Further, the present study provides some evidence of cross-modal transfer of relational responding in rats.

Incrementing non-matching- but not matching-to-sample is rapidly learned in an automated version of the odor span task.

The odor span task (OST) is frequently used to assess memory capacity in rodents. Odor stimuli are presented in a large arena and choices of session-novel odors produce food reward. The procedure can be described as an incrementing non-matching-to-sample contingency because on each trial one new stimulus is presented along with one or more previously presented (non-reinforced) comparison odors. An automated version of this task has recently been developed in which odors are presented with an olfactometer in an operant chamber using a successive conditional discrimination procedure. The present study compared the acquisition of matching- vs. non-matching-to-sample versions of the task with six rats tested under each procedure. All six rats trained on the non-matching variation showed rapid acquisition of the discrimination with high rates of responding to odor stimuli when they were session-novel and low rates of responding to subsequent presentations of those odors. However, only three of the six rats trained on the matching variation met acquisition criteria, and two of the three that did acquire the task required extensive training to do so. These results support findings from the OST that rats can differentiate between stimuli that are session-novel and those previously encountered, but also that a matching contingency is more difficult to learn than a non-matching arrangement. These findings parallel differences observed between acquisition of simple matching- and non-matching-to-sample tasks, but accounts such as novelty preference or the oddity preference effect may not be sufficient to explain the present results.

Effects of NMDA antagonist dizocilpine (MK-801) are modulated by the number of distractor stimuli in the rodent odor span task of working memory.

The rodent odor span task (OST) uses an incrementing non-matching to sample procedure in which a series of odors is presented and selection of the session-novel odor is reinforced. An OST is frequently used to test the effects of neurobiological variables on memory capacity as the number of odors to remember increases during the course of the session. In this regard, one important finding has been that NMDA receptor antagonists selectively impair OST performance at doses that spare accuracy on control tasks. However, in many versions of the odor span task the number of stimuli to remember is confounded with the number of distractor odors presented to the rat on each trial. The present study compared the effects of the NMDA antagonist dizocilpine when the number of choices was held constant at two (one novel odor-S+ and one previously presented distractor odor-S-) and when the number of choice stimuli was permitted to increase up to 10 (one S+ and 9 S-). Dizocilpine impaired OST accuracy at doses that had no effect on a reference memory control task in both 2-choice and 10-choice conditions; however, the dose-response function was shifted to the left in the 10-choice tests. The impairments produced by dizocilpine were exacerbated as the memory load increased in both 2- and 10-choice conditions. These findings support the hypothesis that NMDA antagonism reduces the number of stimuli that rats can remember accurately, but the interaction between the effective DZP dose and the number of distractors shows that drug effects on OST performances may involve attentional factors in addition to memory capacity. The findings also demonstrate that variations in number of OST distractors can be used to alter sensitivity of the task.

Effects of set size on identity and oddity abstract-concept learning in rats.

Match (MTS) and non-match-to-sample (NMTS) procedures are used to assess concepts of identity and oddity across species and are measured by transfer performance to novel stimuli. The number of exemplars used in training (set size) has been shown to affect learning with evidence of larger set sizes promoting concept learning in several species. The present study explored the effects of set size and procedure on concept learning in rats using olfactory stimuli. Concept learning was assessed for 20 rats via transfer tests consisting of novel stimuli after rats were initially trained to either MTS or NMTS with two or ten stimuli as exemplars. No difference was found in acquisition or transfer between MTS and NMTS, but rats trained with ten stimuli performed better on novel transfer tests than rats trained with two. When set size was expanded for rats originally trained with two stimuli and rats were re-tested with ten novel stimuli, performance showed full transfer demonstrating that training with multiple exemplars facilitates concept learning.

Amnestic drugs in the odor span task: Effects of flunitrazepam, zolpidem and scopolamine.

The odor span task is an incrementing non-matching-to-sample procedure designed to provide an analysis of working memory capacity in rodents. The procedure takes place in an arena apparatus and rats are exposed to a series of odor stimuli in the form of scented lids with the selection of new stimuli reinforced. This procedure makes it possible to study drug effects as a function of the number of stimuli to remember. In the present study, the non-selective positive allosteric GABAA receptor modulator flunitrazepam impaired odor span performance at doses that did not affect a control odor discrimination. In contrast, the alpha-1 selective positive GABAA receptor modulator zolpidem and the cholinergic receptor antagonist scopolamine only impaired odor span at doses that produced more global impairment, including decreased accuracy in the control discrimination and increased response omissions in the both the odor span and control discrimination procedures. Even though the effects of flunitrazepam were selective to odor span performance, they did not depend on the number of stimuli to remember-the same degree of impairment occurred regardless of the memory load. These findings suggest that flunitrazepam interfered selectively with conditional discrimination performance rather than working memory and tentatively suggest that flunitrazepam's selective effects in the odor span task relative to the control odor discrimination are mediated by one or more non-alpha1 GABAA receptor subtypes.

Effects of MDMA on olfactory memory and reversal learning in rats.

The effects of acute and sub-chronic MDMA were assessed using a procedure designed to test rodent working memory capacity: the odor span task (OST). Rats were trained to select an odor that they had not previously encountered within the current session, and the number of odors to remember was incremented up to 24 during the course of each session. In order to separate drug effects on the OST from more general performance impairment, a simple olfactory discrimination was also assessed in each session. In Experiment 1, acute doses of MDMA were administered prior to select sessions. MDMA impaired memory span in a dose-dependent fashion, but impairment was seen only at doses (1.8 and 3.0 mg/kg) that also increased response omissions on both the simple discrimination and the OST. In Experiment 2, a sub-chronic regimen of MDMA (10.0 mg/kg, twice daily over four days) was administered after OST training. There was no evidence of reduced memory span following sub-chronic MDMA, but a temporary increase in omission errors on the OST was observed. In addition, rats exposed to sub-chronic MDMA showed delayed learning when the simple discrimination was reversed. Overall, the disruptive effects of both acute and sub-chronic MDMA appeared to be due to non-mnemonic processes, rather than effects on specific memory functions.

Repeated Acquisition in the Morris Swim Task: Effects of MDMA, Methamphetamine and Methylphenidate.

Acute effects of methylenedioxymethamphetamine (MDMA), methamphetamine (MA) and methylphenidate (MPD) were studied using a within-subject, repeated acquisition/performance procedure adapted to the Morris Swim Task. To investigate place learning, the acquisition component consisted of a hidden platform that varied in location across experimental sessions. As a control for drug effects not specific to acquisition, a performance component was included in which the hidden platform was in the same pool location in every experimental session. All three drugs increased escape latencies and swim distances in dose-dependent fashion. However, impairment in the acquisition component was generally observed only at doses that also produced impairment in the performance component, suggesting that effects were not selective to place learning. None of the drugs produced enhancement of learning or performance at any dose. Taken together, the results suggest that acute exposure to these psychomotor stimulants produce global impairment of performance in the Morris task, rather than specific deficits in place learning.

Functional equivalence classes in rats: Repeated olfactory discrimination reversals and delayed stimulus probes.

The simultaneous matching-to-sample procedures that are widely used to study stimulus equivalence in human participants have generally been unsuccessful in animals. However, functional equivalence classes have been demonstrated in pigeons and sea lions using a concurrent repeated reversal discrimination procedure. In this procedure, responding to one set of stimuli is reinforced but responding to a different set is not and the set associated with reinforcement is changed with multiple reversals during the experiment. The experiments reported here were designed to assess whether functional equivalence classes could be demonstrated in rats using similar techniques. Rats were initially trained with two sets of olfactory stimuli (six odors/set). Following many reversals, probe reversal sessions were conducted in which rats were exposed to a subset of the members of each set and, later in the session, the withheld stimuli were introduced. Responding to these delayed probe trials in accord with the reversed contingencies constituted transfer of function. There was some evidence of transfer in Experiment 1, but the effects were relatively weak and variable. Experiment 2 introduced procedural changes and found strong evidence of transfer of function consistent with the formation of functional equivalence classes. These procedures offer a promising strategy to study symbolic behavior in rodents.

Effects of dizocilpine (MK801) on olfactory span in rats.

NMDA receptor antagonists interfere with learning and memory in some tasks, but not others. Some recent accounts have suggested that tasks placing demands on working memory are those most likely to be affected, and the present study tested this hypothesis. The purpose of the study was to adapt a recently developed procedure designed to test working memory capacity, the olfactory memory span task, for use in behavioral pharmacology and to then determine the effects of the NMDA receptor antagonist, dizocilpine (MK801) on performance in this task. Rats were trained in a non-match-to-sample procedure under conditions in which they had to remember an increasing number of olfactory stimuli as the session progressed. Simple olfactory discrimination trials were interspersed to provide a performance control. Effects of dizocilpine (.03, .10, .17, .3mg/kg) were determined after stable performances were obtained. Rats were able to sustain stable performances on both the span and simple discrimination tasks with average spans of about 10 items. Accuracy declined as the number of stimuli to remember increased, and dizocilpine impaired accuracy in a dose-dependent and memory-load dependent fashion. The finding that the effects of dizocilpine interacted with the number of stimuli to remember is generally consistent with hypotheses linking NMDA receptors and working memory processes.

Repeated reversals of concurrent olfactory discriminations in rats: A search for functional equivalence.

Equivalence class formation has been difficult to demonstrate in nonhumans, but one method that has been successful is a simple discrimination procedure in which contingencies associated with two sets of arbitrary discriminative stimuli are repeatedly reversed. Pigeons and sea lions shift responding after encountering the newly-reversed contingency with only a few set members, showing evidence of functional equivalence. We used this strategy to determine whether similar findings would occur in rats using olfactory stimuli. Rats were trained to nose-poke in the presence of six stimuli arbitrarily designated as members of the positive set; responses to the six members of the negative set were not reinforced. When discriminative performance was established, contingencies associated with each set were reversed and re-reversed each time subjects met a performance criterion. All subjects successfully acquired the concurrent simple discriminations and were exposed to between 12 and 60 reversals, but none showed clear evidence of functional class formation until a final procedure in which the stimulus sets that had been in place were arbitrarily rearranged. Acquisition with these new stimulus sets was impaired, showing that class membership generated by the original stimulus sets interfered with learning the new ones, thus providing evidence of functional equivalence.

Successive incrementing non-matching-to-samples in rats: An automated version of the odor span task.

The odor span task is a procedure frequently used to study remembering of multiple stimuli in rodents. A large arena is used and odor stimuli are presented using scented cups. Selection of each odor is reinforced when first presented, but not on subsequent presentations; correct selections depend on remembering which stimuli were previously presented. The use of an arena setting with manual stimulus presentation makes the odor span task labor-intensive and limits experimental control; thus, an automated version of the task would be of value. The present study used an operant chamber equipped with an olfactometer and trained rats using successive conditional discrimination procedures under an incrementing non-matching-to-samples contingency. High rates of responding developed to odor stimuli when they were session-novel with low rates of responding to subsequent presentations of that odor. Additional experiments assessed variations of the procedure to determine the role of the frequency of odor presentation and the retention interval separating sample and comparison. Discrimination was impaired with long retention intervals suggesting the importance of this variable. These findings confirmed that rats differentiate between stimuli that are session-novel and those previously encountered and support the use of an automated procedure as an alternative to the odor span task.

Abstraction, Multiple Exemplar Training and the Search for Derived Stimulus Relations in Animals.

Symmetry and other derived stimulus relations are readily demonstrated in humans in a variety of experimental preparations. Comparable emergent relations are more difficult to obtain in other animal species and seem to require certain specialized conditions of training and testing. This article examines some of these conditions with an emphasis on what animal research may be able to tell us about the nature and origins of derived stimulus relations. We focus on two areas that seem most promising: 1) research generated by Urcuioli's (2008) theory of the conditions necessary to produce symmetry in pigeons, and 2) research that explores the effects of multiple exemplar training on emergent relations. Urcuioli's theory has successfully predicted emergent relations in pigeons by taking into account their apparent difficulty in abstracting the nominal training stimulus from other stimulus properties such as location and temporal position. Further, whereas multiple exemplar training in non-humans has not consistently yielded arbitrarily-applicable relational responding, there is a growing body of literature showing that it does result in abstracted same-different responding. Our review suggests that although emergent stimulus relations demonstrated in non-humans at present have not yet shown the flexibility or generativity apparent in humans, the research strategies reviewed here provide techniques that may permit the analysis of the origins of derived relational responding.

Generalized identity in a successive matching-to-sample procedure in rats: Effects of number of exemplars and a masking stimulus.

Two experiments examined the emergence of generalized identity matching in rats using a successive discrimination procedure with olfactory stimuli. Trials consisted of the presentation of two odors separated by a 1-s interstimulus interval. Responses during the second odor presentation were reinforced only if the two odors were identical. In Experiment 1, rats were trained with two odors and then exposed to sessions that included unreinforced probe trials with novel odors. There was evidence of higher response rates on matching probe trials in some rats, but matching did not approach baseline levels. Additional training with four exemplars produced transfer to novel odors that was equivalent to baseline levels. Experiment 2 tested the possibility that detection of stimulus change, rather than generalized identity, was responsible for the transfer seen in Experiment 1. Thus, a masking odor was inserted during the 1-s interstimulus interval so that stimulus change occurred on all trials. Although response rates on probe trials were lower than baseline rates, above chance transfer to novel stimuli was still observed in four of the five animals tested. These findings support the hypothesis that transfer of matching to novel odors in this successive matching-to-sample paradigm is based on a generalized identity relation.

Effects of N-Methyl-D-aspartate (NMDA) antagonists ketamine, methoxetamine, and phencyclidine on the odor span test of working memory in rats.

The glutamate hypothesis proposes that N-Methyl-D-aspartate (NMDA) receptor hypofunction underlies cognitive and perhaps other schizophrenic symptoms. The present study used the odor span task to assess the effects of NMDA antagonists on remembering multiple stimuli in rodents. This task uses an incrementing nonmatching-to-sample procedure in which responses to a new olfactory stimulus are reinforced on each trial, whereas responses to previously presented stimuli are not. NMDA antagonists have been associated with memory impairments in a variety of animal models; however, there are inconsistencies across different NMDA antagonists and tasks used. The current study compared the acute effects of phencyclidine (PCP), ketamine (KET), and the novel NMDA antagonist methoxetamine (MXE) on responding in the odor span task and a simple discrimination control task. PCP and MXE impaired odor span accuracy at doses that did not impair simple discrimination in most rats; however, the effects of KET were less selective. Within-session analyses indicated that the effects of PCP and MXE depended on the number of stimuli to remember, that is, impairment only occurred when the memory load was relatively high. These effects of PCP and MXE were consistent with the hypothesis that NMDA antagonists may interfere with working memory, but the basis for less selective results with KET are unclear. (PsycINFO Database Record

Successive odor matching- and non-matching-to-sample in rats: A reversal design.

There is a growing body of research on matching- and non-matching-to-sample (MTS, NMTS) relations with rats using olfactory stimuli; however, the specific characteristics of this relational control are unclear. In the current study we examine MTS and NMTS in rats with an automated olfactometer using a successive (go, no-go) procedure. Ten rats were trained to either match- or non-match-to-sample with common scents (apple, cinnamon, etc.) as olfactory stimuli. After matching or non-matching training with four odorants, rats were tested for transfer twice with four new odorants on each test. Most rats trained on MTS showed immediate transfer to new stimuli, and most rats trained on NMTS showed full transfer by the second set of new odors. After meeting criterion on the second transfer test, the contingencies were reversed with four new odor stimuli such that subjects trained on matching were shifted to non-matching and vice versa. Following these reversed contingencies, the effects of the original training persisted for many trials with new odorants. These data extend previous studies on same-different concept formation in rats, showing strong generalization requiring few exemplars. The critical role of olfactory stimuli is discussed.

Olfactory repeated discrimination reversal in rats: effects of chlordiazepoxide, dizocilpine, and morphine.

Effects of a benzodiazepine (chlordiazepoxide), an N-methyl-D-aspartate receptor antagonist (dizocilpine), and an opiate agonist (morphine) were studied with a procedure designed to assess effects of drugs and other manipulations on nonspatial learning in rats. In each session, rats were exposed to 2 different 2-choice odor-discrimination problems with food reinforcement for correct responses. One problem (performance discrimination) remained the same throughout the study. That is, 1 odor was always correct (S+) and the other was never correct (S-). For the other problem (reversal discrimination), stimuli changed every session. Six different odors were used to program the reversal discrimination; on any given session, S+ was a stimulus that had served as S- the last time it had appeared, S- was a stimulus that had been S+ on its last appearance. Thus, in each session, learning a discrimination reversal could be studied along with the performance of a comparable, but previously learned, discrimination. Chlordiazepoxide interfered with reversal learning at doses that had no effect on the performance discrimination. Morphine and dizocilpine also impaired reversal learning but only at doses that also affected performance of the well-learned performance discrimination.

Identity matching-to-sample with olfactory stimuli in rats.

Identity matching-to-sample has been difficult to demonstrate in rats, but most studies have used visual stimuli. There is evidence that rats can acquire complex forms of olfactory stimulus control, and the present study explored the possibility that identity matching might be facilitated in rats if olfactory stimuli were used. Four rats were trained on an identity match-to-sample procedure with odorants mixed in cups of sand as stimuli. Digging in the sample cup produced two comparison cups, and digging in the comparison cup that contained the same scent as the sample was reinforced. When criterion accuracy levels were reached, novel stimuli were added to the baseline training regimen. All 4 rats reached terminal performance of above 90% correct matching with more than 20 different baseline stimuli and matched novel stimulus combinations with above-chance accuracy; 3 of the 4 rats matched novel stimuli at levels significantly above chance. Accurate matching performance was demonstrated both with 2- and 3-comparison procedures. These results suggest that generalized matching-to-sample can be observed in rats when olfactory stimuli are used and, furthermore, that multiple-exemplar training may be important for its emergence.

The distinction between positive and negative reinforcement: use with care.

It is customary in behavior analysis to distinguish between positive and negative reinforcement in terms of whether the reinforcing event involves onset or offset of a stimulus. In a previous article (Baron & Galizio, 2005), we concluded that a distinction of these terms is not only ambiguous but has little if any functional significance. Here, we respond to commentaries by a group of distinguished behavior analysts about the issues we raised. Although several of the commentators argued for preservation of the distinction, we remain unconvinced that its benefits outweigh its weaknesses. Because this distinction is so deeply embedded in the language of behavior analysis, we hardly expect that it will be abandoned. However, we hope that the terms positive and negative reinforcement will be used with circumspection and with full knowledge of the confusion they can engender.

Olfactory Stimulus Control and the Behavioral Pharmacology of Remembering.

Behavior analytic approaches and techniques have much to offer to the study of remembering. There is currently great interest in the development of animal models of human memory processes in order to enhance understanding of the neurobiology of memory and treatment of dementia and related disorders. Because rodent models are so important in contemporary neuroscience and genetics, development of procedures to study various forms of memory in rodents is a point of emphasis. The sense of smell plays an important role in rodent behavior and use of olfactory stimuli has permitted demonstrations of complex forms of stimulus control that have also served as baselines for studying drug effects on remembering. This article focuses on the effects of drugs on behavior maintained by two related procedures: delayed matching-to-sample with odors and the Odor Span Task. These types of procedures provide an opportunity to explore drug effects on behavior maintained by multiple stimuli and across a range of delay intervals with potential to advance analysis of the behavioral pharmacology of remembering.