Amount of training and cue-evoked taste-reactivity responding in reinforcer devaluation

In two experiments, rats received minimal (16) pairings of one auditory conditioned stimulus (CS) cue with a sucrose reinforcer, and extensive (112) pairings of another auditory CS with that reinforcer. After sucrose was devalued by pairing it with lithium chloride in some rats (Devalue groups) but not others (Maintain groups), taste reactivity (TR) and other responses to unflavored water were assessed in the presence of the auditory CSs alone. The minimally trained CS controlled substantially more evaluative TR responses than the extensively trained CS. Those TR responses were hedonic (positive) in the Maintain groups, but aversive (negative) in the Devalue groups. By contrast, food cup entry and other responses thought not to reflect evaluative taste processing were controlled more by the extensively trained cue. These responses were reduced by sucrose devaluation comparably, regardless of the amount of training. The results suggest rapid changes in the content of learning as conditioning proceeds. Early in training, CSs may be capable of activating preevaluative processing of an absent food reinforcer that includes information about its palatability, but that capability is lost as training proceeds.     

Differential involvement of the central amygdala in appetitive versus aversive learning

Understanding the function of the distinct amygdaloid nuclei in learning comprises a major challenge. In the two studies described herein, we used c-Fos immunolabeling to compare the engagement of various nuclei of the amygdala in appetitive and aversive instrumental training procedures. In the first experiment, rats that had already acquired a bar-pressing response to a partial food reinforcement were further trained to learn that an acoustic stimulus signaled either continuous food reinforcement (appetitive training) or a footshock (aversive training). The first training session of the presentation of the acoustic stimulus resulted in significant increases of c-Fos immunolabeling throughout the amygdala; however, the pattern of activation of the nuclei of the amygdala differed according to the valence of motivation. The medial part of the central amygdala (CE) responded, surprisingly, to the appetitive conditioning selectively. The second experiment was designed to extend the aversive versus appetitive conditioning to mice, trained either for place preference or place avoidance in an automated learning system (INTELLICAGE). Again, much more intense c-Fos expression was observed in the medial part of the CE after the appetitive training as compared to the aversive training. These data, obtained in two species and by means of novel experimental approaches balancing appetitive versus aversive conditioning, support the hypothesis that the central nucleus of the amygdala is particularly involved in appetitively motivated learning processes.     

Relations between Pavlovian-instrumental transfer and reinforcer devaluation

Relations between posttraining reinforcer devaluation and Pavlovian-instrumental transfer were examined in 2 experiments. When a single reinforcer was used, extended training of the instrumental response increased transfer but reduced devaluation effects. When multiple instrumental reinforcers were used, both reinforcer-specific transfer and devaluation effects were less influenced by the amount of instrumental training. Finally, although reinforcer devaluation decreased both Pavlovian conditioned responses and baseline instrumental responding, it had no effect on either single-reinforcer or reinforcer-specific transfer. These results indicate that transfer and reinforcer devaluation can reflect different aspects of associative learning and that the nature of associative learning can be influenced by parameters such as the amount of training and the use of multiple reinforcers.     

SELECTIVE ASSOCIATIONS PRODUCED SOLELY WITH APPETITIVE CONTINGENCIES: THE STIMULUS-REINFORCER INTERACTION REVISITED

In studies reporting stimulus-reinforcer interactions in traditional conditioning paradigms, when a tone-light compound was associated with food the light gained stimulus control, but when the compound was paired with shock avoidance the tone gained control. However, the physical nature of the reinforcerrelated events (food vs. shock) presented in the presence of the tone-light compound was always confounded with the conditioned hedonic value of the compound's presence relative to its absence. When the compound was paired with shock, its presence was negative relative to its absence (which was shock-free). In contrast, when the compound was paired with food, its presence was positive relative to its absence (which was food-free). The present experiment dealt with this confounding effect by conditioning a tone-light compound to be positive or negative, relative to its absence, solely with food reinforcement. One group of rats received food for responding in the presence of the tone-light compound and no food in its absence. The other group also responded in the presence of the compound, but received food only in its absence. These rats were trained on a chained schedule in which responding in the presence of the tone-light compound produced a terminal link signaled by the absence of the compound; responding ceased in the terminal link because it delayed food delivery. In a test session to assess stimulus control by the elements of the compound, tone and light were presented separately under extinction conditions. Rats that had been exposed to a positive correlation between food and the compound emitted almost double the responses in the presence of the light as in the presence of the tone. In comparison, rats that had been exposed to a negative correlation emitted only two thirds as many responses in the presence of the light as in the presence of the tone. Because this selective association was produced using only food, it appears that the contingencies under which a reinforcer is presented, rather than (or as well as) its physical properties, can generate the selective associations previously attributed to “stimulus-reinforcer interactions.” This could mean that regardless of the class of reinforcer that ultimately maintains responding (appetitive or aversive), the contingency-generated hedonic value of the compound stimulus may influence the dominant modality of stimulus control.     

Positive conditioned suppression: conditioned suppression using positive reinforcers as the unconditioned stimuli

Research has revealed the phenomenon of conditioned suppression in which the rate of responding is reduced during a stimulus that is paired with noncontingent shock. The present study replicated this procedure, but used noncontingent positive reinforcers instead of the aversive shock. The lever-pressing responses of rats were reinforced with food or water. While the rats were responding, a stimulus was occasionally presented and paired with the delivery of a noncontingent positive reinforcer, which was either food, water, or brain stimulation for different rats. The result was a reduction in the rate of responding during the conditioned stimulus. This finding shows that conditioned suppression occurs during a signal for reinforcing as well as aversive stimuli.     

Complementary roles for the amygdala and hippocampus during different phases of appetitive information processing

Evidence collected from rodent models of memory storage suggests that rapid forms of learning engage the involvement of multiple brain regions each of which may participate in a different component of information processing. The present study used temporary inactivation of the amygdala and hippocampus during different phases of information processing on a one-trial appetitive-conditioning task to examine how these two regions might participate in the storage of appetitive memories. Male Long Evans rats were chronically implanted into the amygdala or dorsal hippocampus and food deprived. Rats were trained on a radial maze conditioned cue preference task where training occurred in one 40-min session and testing took place 24 h later. The amygdala or hippocampus was inactivated separately with muscimol (50 ng/microl) injected immediately before or after training, or immediately before testing. Saline-injected rats displayed a conditioned preference by spending more time in the arm that previously contained food than in the arm that did not contain food. Muscimol injected into the amygdala before training or testing blocked the conditioned preference. Muscimol injected into the hippocampus immediately after training blocked the conditioned preference. These results suggest that the processing of memories may require multiple contributions from separate brain systems for at least short-term (24 h) storage. The resulting output from each system may converge on a similar downstream target to influence behavior.     

Incubation of food craving in rats: A review

Incubation of food craving is an abstinence-dependent increase in responding for reward-paired cues. Incubation of craving was first reported for rats responding for cocaine-paired cues, and later generalized to several drugs of abuse and for food. Incubation of drug and food craving has been reported in clinical studies as well. Incubation of food craving by rats has been reported for standard chow as well as for high fat and sucrose reinforcers. Parametric and other evaluations of the incubation of food craving reveal manipulations that reduce incubation, including environmental enrichment and pharmacological manipulation of dopamine, glutamate, and endogenous opiates. Several brain regions are likely involved in the effect, including mesolimbic terminals and the central nucleus of the amygdala. Further study of the incubation of food craving could facilitate development of treatments for cravings that precede relapse characteristic of drug and food addictions.     

Instrumental performance following reinforcer devaluation depends upon incentive learning

Conditioning an aversion to the reinforcer following instrumental training reduces performance in a subsequent extinction test. Three experiments examined whether this reinforcer-devaluation effect depends upon experience with the devalued reinforcer prior to the extinction test. In Experiments 1 and 2 thirsty rats were trained to press a lever for sucrose solution in a single session. All animals then received an injection of lithium chloride (LiCl) either immediately following the session or after a delay of 6 hr. On the next day either the sucrose solution or water was presented non-contingently either in the operant chamber without the lever present or in a separate drinking cage. In a subsequent extinction test only the animals that had received immediate LiCl and re-exposure to non-contingent sucrose pressed less than those in the delayed-LiCl control groups. Experiment 3 demonstrated that this difference depended, at least in part, on post-conditioning exposure to a contingent reinforcer. Lever pressing and chain pulling were reinforced concurrently with either a sucrose or a sodium chloride solution in a single session immediately before the administration of LiCl. All animals then received non-contingent presentations of one of the reinforcers in the absence of both manipulanda. Finally, performance of both actions was assessed in an extinction test. Re-exposure to a reinforcer produced a relative reduction in the performance of its associated action on test. These results are interpreted as evidence that the instrumental reinforcer devaluation effect depends upon a process of incentive learning.     

Signalling and incentive processes in instrumental reinforcer devaluation

We have previously reported that conditioning an aversion to the reinforcer using an isotonic lithium chloride (LiCl) solution following instrumental training reduces performance in a subsequent extinction test only if animals are re-exposed to the reinforcer prior to the test. Rescorla (1992), in contrast, reported an immediate devaluation effect using a hypertonic LiCl solution that did not depend upon re-exposure. In two experiments we examined the effect of using a hypertonic LiCl solution to condition the aversion to the reinforcer on subsequent instrumental performance in extinction, with and without re-exposure. In Experiment 1 thirsty rats were trained to press a lever for a sucrose solution before being injected with 0.6 M LiCl either immediately or after a delay. Half of the immediate and delay groups were then re-exposed to the sucrose in the absence of the lever, with the remainder being exposed to water. Contrary to the previously reported effects of isotonic LiCl, a hypertonic solution induced a reinforcer devaluation effect in all the immediately poisoned animals, which did not depend upon re-exposure to the reinforcer. In Experiment 2 the possibility that this devaluation effect was induced by the discomfort associated with the hypertonicity of the solution was assessed by replicating Experiment 1 but, in addition, using two immediately poisoned groups given the LiCl injection under anaesthesia. In the absence of anaesthesia, the devaluation effect observed without re-exposure to the reinforcer in Experiment 1 was replicated. When the injection was given under anaesthesia, however, a reinforcer devaluation effect was observed only in animals that were re-exposed to the reinforcer prior to the extinction test. These results were interpreted as evidence that a reinforcer devaluation effect induced by pairing the reinforcer with illness depends upon a process of incentive learning, whereas a devaluation effect mediated by learning a signalling relationship between the reinforcer and somatic discomfort does not.     

Persistence of preference for a flavor presented in simultaneous compound with sucrose

Rats exposed to a simultaneous compound of a flavor and sucrose subsequently exhibited a preference for the flavor over water. This preference persisted across repeated testing even though the flavor was presented in the absence of sucrose. The preference did, however, extinguish if the rats were hungry when trained or tested, or if they had been reexposed to sucrose between training and test. Though failing to extinguish the preference, presentation of the flavor outside the compound protected it from the effects of sucrose devaluation, indicating that these presentations extinguished the within-compound association between the flavor and sucrose. The authors conclude that the hedonic reaction elicited by sucrose imbues the flavor with the same hedonic properties, and these properties maintain the preference independently of the flavor-sucrose association.     

Hedonic and nucleus accumbens neural responses to a natural reward are regulated by aversive conditioning

The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli. Learning can alter the hedonic valence of a given stimulus, and it remains unclear how the NAc encodes this shift. The present study examined whether the population response of NAc neurons to a taste stimulus is plastic using a conditioned taste aversion (CTA) paradigm. Electrophysiological and electromyographic (EMG) responses to intraoral infusions of a sucrose (0.3 M) solution were made in naïve rats (Day 1). Immediately following the session, half of the rats (n = 6; Paired) received an injection of lithium chloride (0.15 M; i.p.) to induce malaise and establish a CTA while the other half (n = 6; Unpaired) received a saline injection. Days later (Day 5), NAc recordings during infusions of sucrose were again made. Electrophysiological and EMG responses to sucrose did not differ between groups on Day 1. For both groups, the majority of sucrose responsive neurons exhibited a decrease in firing rate (77% and 71% for Paired and Unpaired, respectively). Following conditioning, in Paired rats, EMG responses were indicative of aversion. Moreover, the majority of responsive NAc neurons now exhibited an increase in firing rate (69%). Responses in Unpaired rats were unchanged by the experience. Thus, the NAc differentially encodes the hedonic value of the same stimulus based on learned associations.Our search for sustenance and pleasurable stimuli is often balanced by our desire to avoid punishment and harm. Similarly, neural systems responsible for generating approach behavior must be countered by signals that suppress approach behavior under contexts where approach is dangerous or maladaptive (Hoebel et al. 2007). The nucleus accumbens (NAc) is acutely involved in food intake and goal-directed, approach behavior. Pharmacological manipulations of the NAc promote food intake even in sated rats (Maldonado-Irizarry and Kelley 1995; Stratford and Kelley 1997). Lesions or inactivation of the NAc impair conditioned approach behavior (Cardinal et al. 2002; Blaiss and Janak 2009). Interestingly, drugs that lead to inhibition of select regions of the NAc increase positive hedonic responses to palatable taste solutions (Pecina and Berridge 2005). Recordings from individual NAc neurons have mirrored these findings. We and others have shown that consumption of palatable food stimuli is associated with decreases in the firing rate of the majority of responsive NAc neurons (Nicola et al. 2004b; Roitman et al. 2005; Taha and Fields 2005; Wheeler et al. 2008). In addition, decreases in NAc neural activity are associated with bouts of licking behavior for palatable stimuli (Taha and Fields 2006), and disruption of these decreases halt feeding bouts (Krause et al. 2010). Finally, decreases in NAc neural activity are associated with preferred locations previously paired with drug reward (German and Fields 2007). Thus, decreases in NAc activity appear to be closely linked to positive hedonic stimuli, stimuli that have been explicitly paired with them and behavioral approach.The NAc is also responsive to aversive stimuli (Carlezon and Thomas 2009; Levita et al. 2009). The delivery of aversive taste stimuli to rats is associated with increases in the firing rate of the majority of responsive NAc neurons (Roitman et al. 2005; Wheeler et al. 2008). In addition to responding to primary appetitive and aversive taste stimuli, NAc neurons develop responses to predictors of reward and aversion. Individual NAc neurons selectively encode cues that predict either appetitive (Roitman et al. 2005; Day et al. 2006) or aversive (Roitman et al. 2005) stimuli following purely Pavlovian conditioning or a combination of instrumental and Pavlovian conditioning (Setlow et al. 2003; Nicola et al. 2004a). NAc neurons come to encode departure from locations not associated with reward with the majority response being that of excitation (German and Fields 2007). Thus, NAc neurons appear to encode aversive stimuli and withdrawal behavior with increases in activity. These and other findings have led to the recent postulation that reward and aversion are differentially encoded by the activity of NAc neurons (Carlezon and Thomas 2009).Data supportive of the activity hypothesis (Carlezon and Thomas 2009) have been generated by the use of different stimuli to serve as appetitive or aversive primary or predictive stimuli. Thus, selective encoding could be biased by the sensory properties of each stimulus rather than their hedonic valence. When a novel, palatable taste is paired with visceral malaise, a Pavlovian association is made and a conditioned taste aversion (CTA) is established. Subsequent exposure to the once palatable stimulus is met with avoidance or aversion and rejection (Garcia et al. 1974; Schafe et al. 1995). Thus, the same taste stimulus can either be appetitive or aversive, depending on Pavlovian associations. Here, individual NAc neurons were recorded in rats (Paired) before (Day 1) and after a CTA (Day 5) was established and compared with rats that received equal exposure to the same stimuli but in an unpaired manner (Unpaired), and hence no CTA developed. Simultaneously, oro-motor behavior was characterized to provide an index of the associative strength of the taste stimulus. Using this paradigm, we determined that the population response of the NAc does indeed encode hedonic valence.     

Lesions of the rat nucleus basalis magnocellularis disrupt appetitive-to-aversive transfer learning

Rats with selective lesions of the nucleus basalis magnocellularis (NBM) and sham-lesion control animals were tested in an operant appetitive-to-aversive transfer task. We hypothesized that NBM lesions would not affect performance in the appetitive phase, but that performance would be impaired during subsequent transfer to the aversive phase of the task. Additional groups of NBM lesion and control rats were tested in the avoidance condition only, where we hypothesized that NBM lesions would not disrupt performance. These hypotheses were based, on the argument that the NBM is not necessary for simple association learning that does not tax attention. Both the appetitive phase of the transfer task and the avoidance only task depend only on simple associative learning and are argued not to tax attention. Consequently, performance in these tasks was predicted to be spared following NBM lesions. Complex, attention-demanding associative learning, however, is argued to depend on the NBM. Performance, in the aversive phase of the transfer task is both attentionally demanding and associatively more complex than in either the appetitive or aversive tasks alone; thus, avoidance performance in the NBM lesion group was predicted to be impaired following transfer from prior appetitive conditioning. Results supported our hypotheses, with the NBM lesion group acquiring the appetitive response normally, but showing impaired performance following transfer to the aversive conditioning phase of the transfer task. Impairments were not attributable to disrupted avoidance learning per se, as avoidance behavior was normal in the NBM lesion group tested in the avoidance condition only.     

Representation-mediated extinction of conditioned flavor aversions

Conditioned flavor aversions were extinguished by presenting without consequence auditory stimuli that had been previously paired with the aversive flavor. In Experiment 1, rats that received tone-sucrose pairings, then sucrose-lithium chloride (LiCl) pairings, and finally repeated tone-alone presentations showed greater sucrose consumption in subsequent testing than rats that received similar sucrose-LiCl pairings and tone-alone presentations but no initial tone-sucrose pairings. Experiment 2 demonstrated the stimulus specificity of the mediated extinction observed in Experiment 1. In Experiment 3, rats that received first-order light-food and second-order tone-light pairings prior to sucrose-LiCl pairings did not show greater subsequent sucrose consumption when extinction of the second-order tone intervened. These results suggest that conditioned stimulus (CS)-evoked representations of events can substitute for those events themselves in the extinction of previously established associations.     

Acquisition and discrimination of appetitively and aversively conditioned heart rate responses in rhesus monkeys

This report describes the acquisition of a conditional heart rate response to both classical aversive and appetitive conditioning in eight rhesus monkeys(Macaca mulatta). The behavioral paradigm consisted of two discrete one minute tones followed by the corresponding unconditional stimuli,i.e., electric shock or Purina monkey chow. A third tone followed by neither food nor shock served as a discriminative stimulus (DS). The conditional heart rate responses developed in two phases. The first phase was characterized by similar responses to both conditional stimuli and the DS. Control heart rate rose during this period. During the second phase, control heart rate decreased (five animals), the DS response disappeared, and different conditional heart rate patterns to food and shock emerged. The existence of distinct conditional response patterns indicates probable differences in the autonomic nervous regulation of the heart during aversive and appetitive conditioning.     

Lesions of the Rat Nucleus Basalis Magnocellularis Disrupt Appetitive-to-Aversive Transfer Learning

Rats with selective lesions of the nucleus basalis magnocellularis (NBM) and sham-lesion control animals were tested in an operant appetitive-to-aversive transfer task. We hypothesized that NBM lesions would not affect performance in the appetitive phase, but that performance would be impaired during subsequent transfer to the aversive phase of the task. Additional groups of NBM lesion and control rats were tested in the avoidance condition only, where we hypothesized that NBM lesions would not disrupt performance. These hypotheses were based on the argument that the NBM is not necessary for simple association learning that does not tax attention. Both the appetitive phase of the transfer task and the avoidance only task depend only on simple associative learning and are argued not to tax attention. Consequently, performance in these tasks was predicted to be spared following NBM lesions. Complex, attention-demanding associative learning, however, is argued to depend on the NBM. Performance in the aversive phase of the transfer task is both attentionally demanding and associatively more complex than in either the appetitive or aversive tasks alone; thus, avoidance performance in the NBM lesion group was predicted to be impaired following transfer from prior appetitive conditioning. Results supported our hypotheses, with the NBM lesion group acquiring the appetitive response normally, but showing impaired performance following transfer to the aversive conditioning phase of the transfer task. Impairments were not attributable to disrupted avoidance learning per se, as avoidance behavior was normal in the NBM lesion group tested in the avoidance condition only.     

Generalization peak shift in rats under conditions of positive reinforcement and avoidance

Rats were trained to discriminate between two click frequencies. One frequency was associated with either variable-interval food reinforcement (Experiment 1) or free-operant avoidance (Experiment 2). The other frequency was associated with the absence of food in Experiment 1 and the absence of shock in Experiment 2. On a click frequency generalization test, the rats in both experiments showed positive peak shift with the shape of the relative gradients being very similar. This is the first reported instance of peak shift in rats when responding was maintained by an avoidance contingency. Nondifferentially trained controls showed that this shift was due exclusively to associative processes, with nonassociative stimulus factors in themselves apparently making no contribution to increased rates at particular stimulus values. These results show the comparability of appetitive and aversive control and support the position that gradient differences do not result from approach versus avoidance per se.     

Trait emotions and affective modulation of the startle eyeblink: on the unique relationship of trait anger

We examined relationships among individual differences in trait emotions and the emotion-modulated startle-eyeblink response. In particular, we examined the extent to which trait anger, which is negative in valence, would be associated with a pattern of approach motivation in startle eyeblink responses to appetitive stimuli. Self-reported trait emotions were compared with emotion-modulated startle eyeblink responses to auditory probes during appetitive, aversive, and neutral pictures. Results revealed that trait anger, enjoyment, and surprise were each associated with greater blink inhibition to appetitive pictures, indicating an approach motivational response. No other trait emotions were associated with startle eyeblink responses to appetitive or aversive pictures. These results support the idea that trait anger, although experienced as a negative emotion, is associated with an approach-related motivational response to appetitive stimuli at basic, reflexive levels of processing.     

Amygdala circuitry in attentional and representational processes

The amygdala has long been implicated in the display of emotional behavior and emotional information processing, especially in the context of aversive events. In this review, we discuss recent evidence that links the amygdala to several aspects of food-motivated associative learning, including functions often characterized as attention, reinforcement and representation. Each of these functions depends on the operation of separate amygdalar subsystems, through their connections with other brain systems. Notably, very different processing systems seem to be mediated by the central nucleus and basolateral amygdala, subregions of the amygdala that differ in their anatomy and in their connectivity. The basolateral amygdala is involved in the acquisition and representation of reinforcement value, apparently through its connections with ventral striatal dopamine systems and with the orbitofrontal cortex. The dentral nucleus, however, contributes heavily to attentional function in conditioning, by way of its influence on basal forebrain cholinergic systems and on the dorsolateral striatum.     

Discrete and contextual cue alterations eliminate the instrumental appetitive-to-aversive transfer impairment in phenytoin-treated rats

We have shown previously that the antiepileptic phenytoin impairs transfer in an instrumental learning task (Banks et al., 1999). The present study examined the effects of contextual alterations on appetitive-to-aversive transfer performance of rats treated with either phenytoin or tang. Adult rats were tested in tone-signaled appetitive and aversive instrumental tasks, where the animal bar-pressed to obtain a food reward (sugar pellet) or to avoid shock. Rats were trained on the appetitive task for 31 days. Beginning on the twenty-first day, rats were gavaged with either phenytoin or tang twice daily. Animals were then transferred to aversive training, with the phenytoin or tang treatment continuing throughout the 25 testing days. For some animals, contextual changes were introduced as they shifted from appetitive to aversive training, while for other animals these changes were not made. Phenytoin-treated rats that were presented with changes in context as they transferred from the appetitive to the aversive task learned the avoidance response to levels substantially higher than drug-treated rats not presented with the contextual changes. These results indicate that phenytoin impairs avoidance learning following transfer from the appetitive task, and that this impairment can be eliminated by introducing changes in context at the point of transfer. In the tang-treated control subjects, on the other hand, there was no improvement in transfer learning performance associated with the changes in contextual cues. This pattern of results suggests that contextual encoding processes in rats being trained in an instrumental appetitive-to-aversive paradigm are dramatically affected by phenytoin.     

The effects of estradiol on avoidance learning in ovariectomized adult rats

The present study examined the effects of ovariectomy and subsequent estradiol replacement on learning in young adult rats using a set of instrumental avoidance paradigms differing in the nature and extent of prior experience in the learning context. Thus, one group of animals was placed directly into avoidance learning (AV). A second group was trained on an appetitive task first, and then transferred into the aversive context (AP-AV). The third group was exposed to the training context without any specific appetitive response requirement, and then required to learn an active avoidance response (Context-AV). We found that estradiol (OVX+E) impaired avoidance acquisition in all cases relative ovariectomized controls (OVX). In contrast, while avoidance learning is improved following appetitive training or context exposure in both OVX+E and OVX animals, the OVX+E animals profit to a greater extent from the appetitive or context experience than do the OVX controls. We suggest that this difference may be due to enhanced attentional processes or improved hippocampal processing of contextual factors. Thus, estradiol negatively influences simple associative avoidance learning in ovariectomized rats, but appears to promote positive transfer.