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Recent studies have indicated that the lateral habenula (LHb) mediates the association of a conditioned stimulus (CS) with the absence of an unconditioned stimulus (US). We generated a CS-no US association using an explicit unpaired training procedure and evaluated the conditioned inhibitory properties using the modified version of the retardation-of-acquisition procedure, one of the procedures for assessing conditioned inhibition. First, rats in the unpaired group received explicit unpaired light (CS) and food (US) presentations, followed by light-food pairings. Rats in the comparison group received paired training alone. The rats in the two groups showed increased food-cup responses to light over paired training. However, rats in the unpaired group showed a slower acquisition of light and food excitatory conditioning than those in the comparison group. Light acquired conditioned inhibitory properties through explicitly unpaired training, as evidenced by its slowness. Second, we examined the effects of the LHb lesions on the decremental effects of unpaired learning on subsequent excitatory learning. Sham-operated rats exhibited decremental effects of unpaired learning on subsequent excitatory learning, while rats with LHb neurotoxic lesions did not. Third, we tested whether preexposure to the same number of lights presented in the unpaired training retarded the acquisition of subsequent excitatory conditioning. Preexposure to light did not significantly retard the acquisition of subsequent excitatory associations, with no LHb lesion effects. These findings indicate that LHb is critically involved in the association between CS and the absence of US. • Explicitly unpaired learning retards subsequent excitatory learning. • Lateral habenula lesions impair CS-no US association. • CS preexposure does not retard subsequent excitatory learning. [ABSTRACT FROM AUTHOR]

Observational learning is a vital skill for survival. This form of learning has been seen in humans and certain non-human animals. However, the neural circuitry underlying this form of learning is still poorly understood. To better understand the factors underlying successful observation in rats, we employed a task where an observer must base its behavior on that of a demonstrator rat to identify a reward location. A comparison was made of behavior during a social and non-social observation condition. Observers oriented more, responded faster and omitted less responses in the social compared to the non-social condition. Observer performance was also linked to initial orientation, proximity, and the manner in which the demonstrator rat performed the task. Previous work on observational learning encompassed multiple exposures to a single solution over days or weeks. The current method provides data from multiple individual novel observational learning trials, leading to much faster and more robust social learning. This method provides a clearly defined interval in which observation must take place. Allowing for precise tracking of both the observer and demonstrator behavior during the learning period. This study highlights observer and demonstrator interplay in successful observational learning and provides a novel method for analyzing social behavior in rodents. • A novel observation learning paradigm that encompasses multiple individual trials. • The rats showed fast and robust social learning. • Responses were more accurate and faster when observing a conspecific than a cue. • The behavior of the demonstrator rat influenced the performance of the observer rat. • Observer's initial proximity and orientation were related to successful performance. [ABSTRACT FROM AUTHOR]

Appetitive learning has been demonstrated several times using neutral cues or contexts as a predictor of food intake and it has been shown that humans easily learn cued desires for foods. It has, however, never been studied whether internal cues are also capable of appetitive conditioning. In this study, we tested whether humans can learn cued eating desires to negative moods as conditioned stimuli (CS), thereby offering a potential explanation of emotional eating (EE). Female participants were randomly presented with 10 different stimuli eliciting either negative or neutral emotional states, with one of these states paired with eating chocolate. Expectancy to eat, desire to eat, salivation, and unpleasantness of experiencing negative emotions were assessed. After conditioning, participants were brought into a negative emotional state and were asked to choose between money and chocolate. Data showed differential conditioned responding on the expectancy and desire measures, but not on salivation. Specific conditioned effects were obtained for participants with a higher BMI (body mass index) on the choice task, and for participants high on EE on the unpleasantness ratings. These findings provide the first experimental evidence for the idea that negative emotions can act as conditioned stimuli, and might suggest that classical conditioning is involved in EE. [ABSTRACT FROM PUBLISHER]

Food cue reactivity is a strong motivation to eat, even in the absence of hunger. Therefore, food cue reactivity might sabotage healthy eating, induce weight gain and impede weight loss or weight maintenance. Food cue reactivity can be learned via Pavlovian appetitive conditioning: It is easily acquired but the extinction of appetitive responding seems to be more challenging. Several properties of extinction make it fragile: extinction does not erase the original learning and extinction is context-dependent. These properties threaten full extinction and increase the risk of full relapse. Extinction procedures are discussed to reduce or prevent the occurrence of rapid reacquisition, spontaneous recovery, renewal and reinstatement after extinction. A translation to food cue exposure treatment is made and suggestions are provided, such as conducting the exposure in relevant contexts, using occasional reinforcement and targeting expectancy violation instead of habituation. A new hypothesis proposed here is that the adding of inhibition training to strengthen inhibition skills that reduce instrumental responding, might be beneficial to improve food cue exposure effects. [ABSTRACT FROM AUTHOR]

Although eating desires can be easily learned, their extinction appears more difficult. The present two-session study aimed to investigate the role of eating expectancies in the short and longer-term extinction of eating desires. In addition, the relationship between eating desires and conditioned evaluations was examined to test whether they might share a similar mechanism. It was hypothesized that the short-term extinction of eating desires would be more successful after the disconfirmation of eating expectancies (instructed extinction or IE), while resulting in worse longer-term extinction because omission of the food reward during extinction is not surprising. In contrast to the hypotheses, it was found that IE had no effect on the short-term and longer-term extinction of eating desires. Eating desires correlated with conditioned evaluations only to some extent. It is concluded that eating expectancies do not mediate the short-term extinction of conditioned eating desires. In addition, their longer-term extinction does not appear to be facilitated by a greater violation of eating expectancies. This suggests that it might not be necessary to focus on expectancy violation in cue exposure therapy to reduce eating desires. [ABSTRACT FROM AUTHOR]

Present-day environments are replete with tempting foods and the current obesity pandemic speaks to humans' inability to adjust to this. Pavlovian processes may be fundamental to such hedonic overeating. However, a lack of naturalistic Pavlovian paradigms in humans makes translational research difficult and important parameters such as implicitness and acquisition speed are unknown. Here we present a novel naturalistic conditioning task: an image of a neutral object was conditioned to marzipan taste in a single trial procedure by asking the participant to eat the ‘object’ (made from marzipan). Relative to control objects, results demonstrate robust pre- to post-conditioning changes of both subjective ratings and early as well as late event related brain potentials, suggesting contributions of implicit (attentional) and explicit (motivational) processes. Naturalistic single-trial taste-appetitive conditioning is potent in humans and shapes attentional and motivational neural processes that might challenge self-regulation during exposure to tempting foods. Thus, appetitive conditioning processes might contribute to overweight and obesity. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis (PROSPERO registration animal/human studies: CRD42021234793/CRD42021234790) examined the relationship between sleep and appetitive conditioning. Inclusion criteria included: a) appetitive conditioning paradigm; b) measure of conditioning; c) sleep measurement and/or sleep loss; d) human and/etor non-human animal samples; and e) written in English. Searches of seven databases returned 3777 publications. The final sample consisted of 42 studies using primarily animal samples and involving food- and drug-related conditioning tasks. We found sleep loss disrupted appetitive conditioning of food rewards (p < 0.001) but potentiated appetitive conditioning of drug rewards (p < 0.001). Furthermore, sleep loss negatively impacted extinction learning irrespective of the reward type. Post-learning sleep was associated with increases in REM sleep (p = 0.02). Findings suggest sleep loss potentiates the impact of psychoactive substances in a manner likely to produce an increased risk of problematic substance use. In obese/overweight populations, sleep loss may be associated with deficits in the conditioning and extinction of reward-related behaviours. Further research should assess the relationship between sleep and appetitive conditioning in humans. • Sleep is an overlooked mechanism underpinning maladaptive appetitive conditioning. • This review examined the relationship between sleep and appetitive conditioning. • Sleep loss disrupts food-related, but potentiates drug-related, reward conditioning. • Post-learning increases in REM sleep are associated with improved task performance. [ABSTRACT FROM AUTHOR]

Background and objectives Successful long-term dieting appears to be difficult, and part of its difficulty might be explained by processes related to classical appetitive conditioning. Increasing the speed of extinction of appetitive responses to food cues and decreasing the magnitude of returns of these responses could help increase the long-term effectiveness of weight loss attempts. Two extinction techniques hypothesized to slow down rapid reacquisition of conditioned appetitive responses were investigated: the provision of 1) occasional reinforced extinction trials (OR) and 2) unpaired unconditioned stimuli (USs) during extinction (UNP). Methods After acquisition, participants (N = 90) received one of three extinction trainings: OR, UNP, or normal extinction (control), followed by a reacquisition phase. Their desire to eat, US expectancy, and salivation were measured. Effects of impulsivity on different phases of appetitive conditioning were also assessed. Results It was found that both extinction techniques were successful in reducing the rate of reacquisition of US expectancies. Participants in the OR condition also demonstrated a slower extinction of US expectancies and desires to eat. However, the reacquisition of conditioned desires was not affected by either extinction technique. Impulsivity did not moderate responses during acquisition or extinction, but appeared to slow down the reacquisition of conditioned desires. Limitations US expectancies and eating desires were not completely extinguished, and a few differences in baseline responses caused difficulty in interpreting some of the findings. Conclusions It is concluded that the provision of occasional reinforced extinction trials and unpaired USs seem promising techniques to slow down reacquisition, but that additional studies are needed. [ABSTRACT FROM AUTHOR]

Objective: Emotional eating has been suggested to be a learned behaviour; more specifically, classical conditioning processes might be involved in its development. In the present study we investigated whether a negative mood facilitates appetitive conditioning and whether trait impulsivity influences this process. Method: After undergoing either a negative or neutral mood induction, participants were subjected to a differential classical conditioning procedure, using neutral stimuli and appetizing food. Two initially neutral distinctive vases with flowers were (CS+) or were not (CS−) paired with chocolate mousse intake. We measured participants' expectancy and desire to eat (4 CS+ and 4 CS− trials), salivation response, and actual food intake. The BIS-11 was administered to assess trait impulsivity. Results: In both mood conditions, participants showed a classically conditioned appetite. Unexpectedly, there was no evidence of facilitated appetitive learning in a negative mood with regard to expectancy, desire, salivation, or intake. However, immediately before the taste test, participants in the negative mood condition reported a stronger desire to eat in the CS+ compared to the CS− condition, while no such effect occurred in the neutral group. An effect of impulsivity was found with regard to food intake in the neutral mood condition: high-impulsive participants consumed less food when presented with the CS+ compared to the CS−, and also less than low-impulsive participants. Discussion: An alternative pathway to appetitive conditioning with regard to emotions is that it is not the neutral stimuli, but the emotions themselves that become conditioned stimuli and elicit appetitive responses. [ABSTRACT FROM AUTHOR]

The amygdala, prefrontal cortex, striatum and other connected forebrain areas are important for reward-associated learning and subsequent behaviors. How these structurally and functionally dissociable regions are recruited during initial learning, however, is unclear. Recently, we showed amygdalar nuclei were differentially recruited across different stages of cue-food associations in a Pavlovian conditioning paradigm. Here, we systematically examined Fos induction in the forebrain, including areas associated with the amygdala, during early (day 1) and late (day 10) training sessions of cue-food conditioning. During training, rats in the conditioned group received tone-food pairings, while controls received presentations of the tone alone in the conditioning chamber followed by food delivery in their home cage. We found that a small subset of telencephalic and hypothalamic regions were differentially recruited during the early and late stages of training, suggesting evidence of learning-induced plasticity. Initial tone-food pairings recruited solely the amygdala, while late tone-food pairings came to induce Fos in distinct areas within the medial and lateral prefrontal cortex, the dorsal striatum, and the hypothalamus (lateral hypothalamus and paraventricular nucleus). Furthermore, within the perifornical lateral hypothalamus, tone-food pairings selectively recruited neurons that produce the orexigenic neuropeptide orexin/hypocretin. These data show a functional map of the forebrain areas recruited by appetitive associative learning and dependent on experience. These selectively activated regions include interconnected prefrontal, striatal, and hypothalamic regions that form a discrete but distributed network that is well placed to simultaneously inform cortical (cognitive) processing and behavioral (motivational) control during cue-food learning. [ABSTRACT FROM AUTHOR]

Animals and humans can easily learn to associate an initially neutral cue with food intake through classical conditioning, but extinction of learned appetitive responses can be more difficult. Intermittent or partial reinforcement of food cues causes especially persistent behaviour in animals: after exposure to such learning schedules, the decline in responding that occurs during extinction is slow. After extinction, increases in responding with renewed reinforcement of food cues (reacquisition) might be less rapid after acquisition with partial reinforcement. In humans, it may be that the eating behaviour of some individuals resembles partial reinforcement schedules to a greater extent, possibly affecting dieting success by interacting with extinction and reacquisition. Furthermore, impulsivity has been associated with less successful dieting, and this association might be explained by impulsivity affecting the learning and extinction of appetitive responses. In the present two studies, the effects of different reinforcement schedules and impulsivity on the acquisition, extinction, and reacquisition of appetitive responses were investigated in a conditioning paradigm involving food rewards in healthy humans. Overall, the results indicate both partial reinforcement schedules and, possibly, impulsivity to be associated with worse extinction performance. A new model of dieting success is proposed: learning histories and, perhaps, certain personality traits (impulsivity) can interfere with the extinction and reacquisition of appetitive responses to food cues and they may be causally related to unsuccessful dieting. [ABSTRACT FROM AUTHOR]

Early-life social adversity, such as child neglect and institutionalized rearing, is associated with later-life difficulties of inhibitory control that may reflect altered attribution of salience to external stimuli. Studies in rats demonstrate that early-life social deprivation results in enhanced responsiveness to reward stimuli and conditioned reward cues. This study examined whether these effects are related to fundamental changes in appetitive conditioning processes involving instrumental goal-directed and habitual responding for food reward. Rats were reared either by the mother (maternal rearing; MR) or in complete isolation from the mother and litter (artificial rearing; AR) and tested as adults in two appetitive conditioning tasks. AR and MR rats did not differ in the amount of goal-directed effort they exerted to obtain food reward on progressive ratio schedules of reinforcement. AR and MR rats also did not differ in the shift from goal-directed to habitual responding on a random interval schedule and they were equally sensitive to changes in reward value. The major difference between AR and MR rats was that AR rats exhibited more non-instrumental responses (empty food magazine entries, ineffective lever presses). Thus, early-life social deprivation of rats through AR affects the expression of unreinforced extraneous behaviors when motivational requirements are high, but does not affect conditioned goal-directed and habitual responding to reward. The findings have implications for understanding what aspects of responsiveness to external stimuli may be selectively affected in disorders of inhibition associated with early-life social adversity. [ABSTRACT FROM AUTHOR]

Olfactory learning in blood-feeding insects, such as mosquitoes, could play an important role in host preference and disease transmission. However, standardised protocols allowing testing of their learning abilities are currently lacking, and how different olfactory stimuli are learned by these insects remains unknown. Using a Pavlovian conditioning paradigm, we trained individuals and groups of Aedes aegypti mosquitoes to associate an odorant conditioned stimulus (CS) with a blood-reinforced thermal stimulus (unconditioned stimulus; US). Results showed, first, that mosquitoes could learn the association between L-lactic acid and the US, and retained the association for at least 24 h. Second, the success of olfactory conditioning was dependent upon the CS - some odorants that elicited indifferent responses in naïve mosquitoes, such as L-lactic acid and 1-octen-3-ol, were readily learned, whereas others went from aversive to attractive after training (Z-3-hexen-1-ol) or were untrainable (ß-myrcene and benzyl alcohol). Third, we examined whether mosquitoes' ability to learn could interfere with the action of the insect repellent DEET. Results demonstrated that pre-exposure and the presence of DEET in the CS reduced the aversive effects of DEET. Last, the nature of the formed memories was explored. Experiments using cold-shock treatments within the first 6 h posttraining (for testing anaesthesia-resistant memory) and a protein synthesis inhibitor (cycloheximide; to disrupt the formation of longterm memory) both affected mosquitoes' performances. Together, these results show that learning is a crucial component in odour responses in A. aegypti, and provide the first evidence for the functional role of different memory traces in these responses. [ABSTRACT FROM AUTHOR]

Highlights: [•] The literature on human reconsolidation is reviewed and discussed. [•] Methods of memory reactivation to induce reconsolidation are discussed. [•] The rationale behind the clinical interest of reconsolidation studies is discussed. [Copyright &y& Elsevier]

To study the heritability of different training stages of appetitive operant conditioning, we carried out behavioural screening of 5 standard inbred mouse strains, 28 recombinant-inbred (BxD) mouse lines and their progenitor strains C57BL/6J and DBA/2J. We also computed correlations between successive training stages to study whether learning deficits at an advanced stage of operant conditioning may be dissociated from normal performance in preceding phases of training.The training consisted of two phases: an operant nose poking phase, in which mice learned to collect a sucrose pellet from a food magazine by nose poking, and an operant lever press and nose poking phase, in which mice had to execute a sequence of these two actions to collect a food pellet. As a measure of magazine oriented exploration, we also studied the nose poke entries in the food magazine during the intertrial intervals at the beginning of the first session of the nose-poke training phase.We found significantly heritable components in initial magazine checking behaviour, operant nose-poking and lever press-nose poking. Performance levels in these phases were positively correlated, but several individual strains were identified that showed poor lever press-nose poking while performing well in preceding training stages. Quantitative trait loci mapping revealed suggestive likelihood ratio statistic peaks for initial magazine checking behaviour and lever press – nose poking. These findings indicate that consecutive stages towards more complex operant behavior show significant heritable components, as well as dissociability between stages in specific mouse strains. These heritable components may reside in different chromosomal areas.

Highlights: [•] Humans easily learn to associate a context with food intake. [•] This context caused an increased desire for food and more positive evaluations. [•] An involvement of preparatory responses of the body was demonstrated. [•] Impulsivity increased susceptibility to overeat in a food-associated context. [ABSTRACT FROM AUTHOR]

Animal experiments provide evidence that learning to associate an auditory stimulus with a reward causes representational changes in auditory cortex. However, most studies did not investigate the temporal formation of learning-dependent plasticity during the task but rather compared auditory cortex receptive fields before and after conditioning. We here present a functional magnetic resonance imaging study on learning-related plasticity in the human auditory cortex during operant appetitive conditioning. Participants had to learn to associate a specific category of frequency-modulated tones with a reward. Only participants who learned this association developed learning-dependent plasticity in left auditory cortex over the course of the experiment. No differential responses to reward predicting and nonreward predicting tones were found in auditory cortex in nonlearners. In addition, learners showed similar learning-induced differential responses to reward-predicting and nonreward-predicting tones in the ventral tegmental area and the nucleus accumbens, two core regions of the dopaminergic neurotransmitter system. This may indicate a dopaminergic influence on the formation of learning-dependent plasticity in auditory cortex, as it has been suggested by previous animal studies. Hum Brain Mapp 34:2841-2851, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Memory reconsolidation has been observed across species and in a number of behavioral paradigms. The majority of memory reconsolidation studies have been carried out in Pavlovian fear conditioning and other aversive memory settings, with potential implications for the treatment of post-traumatic stress disorder. However, there is a growing literature on memory reconsolidation in appetitive reward-related memory paradigms, including translational models of drug addiction. While there appears to be substantial similarity in the basic phenomenon and underlying mechanisms of memory reconsolidation across unconditioned stimulus valence, there are also notable discrepancies. These arise both when comparing aversive to appetitive paradigms and also across different paradigms within the same valence of memory. We review the demonstration of memory reconsolidation across different aversive and appetitive memory paradigms, the commonalities and differences in underlying mechanisms and the conditions under which each memory undergoes reconsolidation. We focus particularly on whether principles derived from the aversive literature are applicable to appetitive settings, and also whether the expanding literature in appetitive paradigms is informative for fear memory reconsolidation. [ABSTRACT FROM AUTHOR]

Intertidal fishes have elaborated spatial cognitive abilities. In this study, we developed an appetitive conditioning paradigm for an intertidal fish species (the chameleon goby; Tridentiger trigono-cephalus) that involves spatial components and ethologically relevant cue stimuli. The gobies rapidly acquired the conditioned anticipatory behaviour after only a few trials of paired presentations of virtual tidal changes and food rewards (which were only available in specific locations during a simulated high tide). The conditioned responses were retained after exposure to a 1 month period without trainings or tidal changes. The rapid acquisition and long-term retention of the conditioned responses indicates that the learning paradigm, which used a combination of water level changes and food availability in specific spatial locations, is biologically significant for this species. Taken together, these results suggest that spatial tasks combined with virtual tidal changes provide a suitable paradigm for evaluating spatial cognitive mechanisms in intertidal fishes. [ABSTRACT FROM AUTHOR]

In each of three experiments animals received blocking, A+ AX+. in which food was always presented after one stimulus, A, that was occasionally accompanied by another stimulus. X. They also received a simple discrimination, AX+ BX-. in which the presence and absence of food was signaled by two compounds that contained one unique cue, A or B, and one common cue, X. In each of these designs, X can be said to be redundant relative to A as a signal for food. Test trials at the end of training revealed that responding during X was stronger after blocking than after the simple discrimination. These results contradict predictions from theories of learning that assume changes in associative strength of a stimulus are determined by a global error term based on the outcome predicted by all the stimuli that are present for a conditioning trial. The results are interpreted, instead, by assuming either that animals store a memory of every trial to which they have been exposed, or that learning is governed by an error term based on the significance of individual stimuli. [ABSTRACT FROM AUTHOR]

Abstract: Two experiments examined temporally based changes in the conditioned magazine-entries of rats when a target food pellet arrived at a fixed time before the termination of a conditioned stimulus. Both experiments found that increasing the rate of intertrial pellets systematically interfered with the rate of acquisition. When intertrial pellets were featured in acquisition, their omission on test trials also resulted in a very poorly expressed conditioned response. On test trials preceded by intertrial pellets, however, peak times in groups trained with intertrial pellets were shifted in a rightward direction under a long but not short interstimulus interval. This rightward shift was accompanied by a smaller standard deviation. Our key findings are best accommodated by real-time associative models. [Copyright &y& Elsevier]

In two experiments, rats received preexposure to one type of food followed by autoshaping in which presentation of one lever was associated with the preexposed food, and presentation of another lever with a novel type of food pellet. In both it was found that acquisition of the leverpress response occurred more readily on the lever associated with the novel food. This example of the US (unconditioned stimulus) preexposure effect is not to be explained in terms of the development of competing responses during preexposure. Explanations in terms of blocking by contextual cues and of habituation to the US are considered. [ABSTRACT FROM AUTHOR]

Ample evidence suggests that, when reactivated by a reminder, a consolidated memory may return to a labile state and needs to be stabilized again in order to persist, a process known as reconsolidation. In a previous study, performed in the crab Chasmagnathus, we found a dual role for the biogenic amine octopamine (OA) during memory consolidation. On the one hand, it was necessary for appetitive memory formation and, on the other, it had a deleterious effect on aversive memory consolidation. Thus, OA could be a good candidate to dissect the neurochemical mechanisms of appetitive and aversive reconsolidation. Here, we initially characterized the reconsolidation of an appetitive memory. Then, we compared appetitive reconsolidation with its aversive counterpart regarding the implication of OA in these processes, and contrasted them with previous findings obtained in the consolidation phase. Our results demonstrate that appetitive reconsolidation takes place when animals are re-exposed to the training context, as shown by the amnesic effect of cycloheximide when applied before the reminder. In addition, the no-reinforcement during the reminder is a necessary condition for appetitive reconsolidation to occur. Remarkably, appetitive reconsolidation is neither impaired by OA receptor antagonists nor facilitated by exogenous OA, whereas aversive reconsolidation can be interfered with by OA administration. Thus, our results indicate that appetitive reconsolidation does not involve OA signaling, while aversive reconsolidation is negatively modulated by OA. All in all, these results could constitute a step towards the identification of particular features of appetitive and aversive reconsolidation. [ABSTRACT FROM AUTHOR]

Abstract: Adolescence is a critical transition period, during which fundamental changes prepare the adolescent for becoming an adult. Heuristic models of the neurobiology of adolescent behavior have emerged, promoting the central role of reward and motivation, coupled with cognitive immaturities. Here, we bring focus to two basic sets of processes, attention and conditioning, which are essential for adaptive behavior. Using the dual-attention model developed by , which identifies a stimulus-driven and a goal-driven attention network, we propose a balance that favors stimulus-driven attention over goal-driven attention in youth. Regarding conditioning, we hypothesize that stronger associations tend to be made between environmental cues and appetitive stimuli, and weaker associations with aversive stimuli, in youth relative to adults. An attention system geared to prioritize stimulus-driven attention, together with more powerful associative learning with appetitive incentives, contribute to shape patterns of adolescent motivated behavior. This proposed bias in attention and conditioning function could facilitate the impulsive, novelty-seeking and risk-taking behavior that is typical of many adolescents. [Copyright &y& Elsevier]

Abstract: Previous research has shown that a nicotine conditional stimulus (CS) can compete with (i.e., overshadow) a brief light CS. Another form of competition, blocking, has not yet been examined with the nicotine CS. Groups of rats were assigned to an element training condition. For the N+ group, during each daily 2h element training session, there were ten intravenous nicotine infusions (0.03mg/kg) followed 30s later with 4s access to sucrose. In the N− group, nicotine and sucrose presentations were explicitly unpaired. The chamber alone group (C alone) had no stimulus presentations. Element training was followed by compound training in all groups. A 30-s houselight was included during the time between the nicotine infusion and paired sucrose delivery. Non-reinforced element presentations assessed relative control of the goal tracking conditioned response (CR). The N+ group showed a higher proportion of CR control by the nicotine than the light. The opposite pattern was found in the N− and C alone groups indicating that nicotine CS controlled less of the CR than the light. Thus, excitatory conditioning with the nicotine CS blocked later conditioning to the light. This finding adds to literature examining the interaction between interoceptive drug CSs and other environmental stimuli. [Copyright &y& Elsevier]

Locusts can learn associations between olfactory stimuli and food rewards, and use the acquired memories to choose between foods according to their nutrient requirements. They are a model system for both the study of olfactory coding and insect nutritional regulation. Previous studies have used operant paradigms for conditioning freely moving locusts, restricting the study of the neural mechanisms underlying the acquisition of olfactory memories, which requires restrained preparations for electrophysiological recordings. Here we present two complementary paradigms for the classical conditioning of olfactory memories in restrained desert locusts (Schistocerca gregaria). These paradigms allow precise experimental control over the parameters influencing learning. The first paradigm is based on classical (Pavlovian) appetitive conditioning. We show that opening of the maxillary palps can be used as a measure of memory acquisition. Maxillary palp opening in response to odour presentation is significantly higher in locusts trained with paired presentation of an odour and a food reward than in locusts trained either with unpaired presentation of food and odour or the odour alone. The memory formed by this conditioning paradigm lasts for at least 24h. In the second paradigm, we show that classical conditioning of an odour memory in restrained locusts influences their decisions in a subsequent operant task. When locusts that have been trained to associate an odour with a food reward are placed in a V-maze, they choose the arm containing that odour significantly more often than naïve locusts. A single conditioning trial is sufficient to induce a significant bias for that odour for up to 4h. Multiple- and block-trial training induce a significant bias that lasts at least 24h. Thus, locusts are capable of forming appetitive olfactory memories in classical conditioning paradigms and can use these memories to modify their decisions. [ABSTRACT FROM AUTHOR]

Abstract: Environmental enrichment is associated with enhanced learning of complex tasks, attenuated seeking of natural and drug rewards, and altered function of the nucleus accumbens (NAcc), a brain region involved in goal-directed behavior. For example, during acquisition of a discriminative learning task, neurons in the NAcc core subregion are more responsive to discrete, goal-directed movements in rats raised in an enriched condition (EC) relative to an isolated condition (IC), but as learning materialized, this enhanced responsiveness shifts to the cues that predict these movements. Here, we report that these results do not extend to NAcc shell: neuronal responses in this subregion are similar in EC and IC rats during goal-directed movement and the presentation of associative cues both during and after task acquisition. With experience in this task, however, the overall proportion of task-related neuronal responses in NAcc shell decreases. The response pattern of shell neurons is also sensitive to the presence of contextual cues: shell neuronal firing reveals a significant shift from a predominant excitatory to a predominant inhibitory profile in probe trials when the cue that predicts sucrose availability is absent. Collectively, these data suggest that NAcc shell neurons encode cues associated with natural reward, are less responsive during appetitive behavior in familiar conditions, and are insensitive to appetitive learning differences expressed in rats reared in different environmental conditions. [Copyright &y& Elsevier]

Abstract: The present study examines two novel aspects of appetitive processing and conditioning: the electrophysiological response to (a) the appetitive taste of a sweet fluid and (b) appetitively/taste conditioned visual stimuli. Event-related potentials (ERPs) were recorded from 32 subjects while they performed a taste conditioning task, in which two symbols were paired with a sweet or a neutral fluid. The results show a clear P1/N1/P2 complex, and a late positive potential (P3) with maxima at right fronto-central electrode sites, in response to the taste stimuli. Of these components particularly the P3 showed robust differences between the sweet and neutral taste. In addition, the electrophysiological response to the taste conditioned stimuli (CS), also showed the expected differences for both P2 and P3 at frontocentral electrodes. The present data demonstrate that the employed paradigm is a useful methodology to study the electrophysiological responses to unconditioned appetitive stimuli. Since appetitive conditioning is assumed to be disturbed in many psychopathological conditions, such as substance dependence, depression and eating disorders, this paradigm could be employed to get more insight in these conditions in humans. [Copyright &y& Elsevier]

Abstract: Ethanol''s motivational consequences have been related to the actions of acetaldehyde, a metabolic product of ethanol oxidation. The present study assessed the role of acetaldehyde in the motivational effects of ethanol on preweanling rats. In Experiment 1 pups (postnatal days 13–14, PD 13–14) were given systemic administration of d-penicillamine (DP, a drug that sequesters acetaldehyde: 0, 25, 50 or 75mg/kg) before pairings of 1.0g/kg ethanol and a rough surface (sandpaper, conditioned stimulus, CS). At test, pups given sandpaper–ethanol pairings exhibited greater preference for the CS than unpaired controls, but this preference was not expressed by pups given DP. Pre-training administration of 25 or 50mg/kg DP completely blocked the expression of ethanol-mediated appetitive conditioning. d-penicillamine did not alter blood ethanol levels. Subsequent experiments revealed that ethanol-induced activation was blocked by central (intra-cisterna magna injections, volume: 1μl, dose: 0 or 75μg) but not systemic treatment with DP (0, 25, 50 or 75mg/kg; ip). These results indicate that: (a) preweanling rats are sensitive to the reinforcing effect of ethanol, and (b) that this effect is associated with the motor activating effect of the drug. These effects seem to be mediated by the first metabolite of ethanol, acetaldehyde. [Copyright &y& Elsevier]

There is evidence to suggest that neurotensin (NT) may enhance cognitive function. For example, in aversive trace conditioning, the NT agonist PD149163 selectively increased trace conditioning (Grimond-Billa, et al., 2008). The present study, therefore, examined the role of NT in associative learning, tested using an appetitive trace conditioning procedure (0-s or 10-s inter-stimulus-interval [ISI]) with a mixed frequency noise as a conditioned stimulus (CS) and food delivery as the unconditioned stimulus (UCS). The effects of an NT agonist (PD149163, 0.125 and 0.25 mg/kg, Experiment 1) and an NT antagonist (SR142948A, 0.01 and 0.1 mg/kg, Experiment 2) were compared. To take nonspecific effects of these compounds into account, conditioning to the CS was measured as a percentage of total responding, during UCS deliveries and in the intertrial- interval (ITI). In both experiments, associative learning to the contiguously (0-s) presented CS was demonstrated, although there was a relative reduction in this learning under 0.125 mg/kg PD149163. Counter to prediction, the only effect on trace conditioning was some overall reduction in responding to the CS in the 10-s group conditioned under 0.25 mg/kg PD149163. The NT antagonist was without any effect on appetitive conditioning. However, these NT compounds were not ineffective: decreases and increases in responding in the ITI, ISI and during UCS deliveries seen under PD149163 and SR142948A were dissociable from effects on discrete cue conditioning. [ABSTRACT FROM AUTHOR]

The cannabinoid CB1 receptor antagonist/inverse agonist rimonabant (SR 141716) has been shown to block reinforcing and rewarding effects of nicotine. Research has not investigated whether the cannabinoid system is involved in the interoceptive stimulus effects of nicotine functioning as a conditional stimulus (CS). We examined the effects of rimonabant and the CB1/2 receptor agonist, CP 55,940, on responding evoked by a nicotine CS in rats. Additionally, we determined whether CP 55,940 functioned as a CS or a Pavlovian positive drug feature Pavlovian discrimination training involved intermixed nicotine (0.2 mg base/kg) and saline sessions with intermittent access to water only on nicotine. Antagonism tests with rimonabant (0.1-3 mg/kg) and substitution tests with CP 55,940 (0.003–0.1 mg/kg) followed. An effective dose of CP 55,940 was tested against the nicotine generalization curve. A separate group received CS training with CP 55,940 (0.01 mg/kg). Two other groups were trained using CP 55,940 (0.01 or 0.03 mg/kg) as a positive drug feature in which a brief light CS signaled access to water only on CP 55,940 sessions Rimonabant blocked nicotine-evoked responding. CP 55,940 partially substituted for nicotine and enhanced responding to lower nicotine doses. Overall, CP 55,940 did not acquire control of conditioned responding in either Pavlovian drug discrimination task The cannabinoid system was involved in the CS effects of nicotine. This finding is counter to the operant drug discrimination research with nicotine as a discriminative stimulus, warranting further research into this possible dissociation. [ABSTRACT FROM AUTHOR]

Abstract: It has been difficult to find conditioned preference for tactile cues paired with ethanol intoxication in rats. Toward understanding the ontogeny of ethanol reinforcement, we aimed at establishing a simple and reliable procedure for (1) assessing primary appetitive conditioning to ethanol in infant rats and (2) discerning the role the opioid system plays in ethanol-mediated conditioning at this age. Experiment 1 determined the parameters (i.e., dose, interval of conditioning) for assessing ethanol-mediated conditioning. Pups were then trained with differential Pavlovian conditioning (Experiments 2 and 3) in which ethanol intoxication (1.0–2.0g/kg, intragastrically or intraperitoneally delivered) was paired with a tactile stimulus (sandpaper) while an alternative texture signaled the absence of ethanol''s effects. Unpaired control conditions were also used. Tactile preferences were assessed after two conditioning sessions. Paired rats spent significantly more time on sandpaper than unpaired controls, an effect that was greater after intragastric administration of 1.0 than 2.0g/kg ethanol. This effect was replicated in Experiments 4a and 4c and found to be inhibited by pretreatment with general (naloxone [NAL]) or specific (d-Pen-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 [CTOP] and naltrindole) opioid antagonists. Blood ethanol levels at conditioning were not altered by NAL (Experiment 4b). The study outlines a procedure that reveals appetitive conditioning to ethanol by infant rats. The results are discussed in terms of a potential ethanol-induced activation of the endogenous opioid system during the onset of the intoxication process. [Copyright &y& Elsevier]

Abstract: The nucleus accumbens (NAc) is important for the ability of motivationally significant stimuli to guide behavior. To further delineate its role in appetitive Pavlovian conditioning, we tested the hypothesis that the NAc contributes to memory consolidation and expression for a goal-tracking version of Pavlovian conditioned approach (PCA) in rats. We found that neither post-training reversible inactivation with the GABA receptor agonists muscimol and baclofen nor inhibition of protein synthesis with anisomycin (ANI) in either the core or shell regions of the NAc had an effect on approach to a reward port in response to a reward-predictive cue (conditioned stimulus, CS+). In contrast, pre-test reversible inactivation of both the core and shell decreased conditioned responding during the CS+. Unlike inactivation of the core, however, reversible inactivation of the shell also produced an increase in responding during the CS− and the inter-trial interval. This suggests that the NAc is not involved in the consolidation of goal-tracking PCA, but that once the memory is formed, the core is required for expression of the CS–unconditioned stimulus (US) association and the shell is required to inhibit conditioned approach behavior at times when the CS+ is not presented. [Copyright &y& Elsevier]

Abstract: Background: Recent theories suggest that extinction is, at least partly, new learning suppressing original associations between a conditioned stimulus and a conditioned response without severing those associations. During extinction alcohol via its effects on inhibitory control may reduce the ability to suppress the original associations between a conditioned stimulus and a conditioned response leading to an impairment of extinction learning. Thus, the present study is set out to examine the effects of alcohol on extinction learning to enhance current knowledge on mechanisms of extinction and conditions that might hamper extinction, which is an important aspect for the treatment of alcohol-dependent patients. Methods: Light to moderate social drinkers (N =32) acquired an instrumental reward seeking response. Extinction training of the reward seeking response was performed after administration of a dose of 0.8g/kg alcohol resulting in a peak blood alcohol concentration ranging from 112 to 184mg/dL. In addition, we assessed subjective alcohol effects and administered a Stop-Signal task which measures the ability to inhibit a pre-potent motor response. Results: Alcohol influenced subjective ratings of light-headedness and increased the Stop-Signal reaction time indicating disinhibiting effects. However, our results did not show any impairment of learning of extinction after the administration of alcohol. Behavioural as well as attentional responses indicated extinction of conditioned responses for both experimental groups. Conclusions: These findings suggest that alcohol at a dose that impairs performance in a task of inhibitory control does not impair learning of extinction. [Copyright &y& Elsevier]

Abstract: The motivational effects of drugs play a key role during the transition from casual use to abuse and dependence. Ethanol reinforcement has been successfully studied through Pavlovian and operant conditioning in adult rats and mice genetically selected for their ready acceptance of ethanol. Another model for studying ethanol reinforcement is the immature (preweanling) rat, which consumes ethanol and exhibits the capacity to process tactile, odor and taste cues and transfer information between different sensorial modalities. This review describes the motivational effects of ethanol in preweanling, heterogeneous non-selected rats. Preweanlings exhibit ethanol-mediated conditioned taste avoidance and conditioned place aversion. Ethanol''s appetitive effects, however, are evident when using first- and second-order conditioning and operant procedures. Ethanol also devalues the motivational representation of aversive stimuli, suggesting early negative reinforcement. It seems that preweanlings are highly sensitive not only to the aversive motivational effects of ethanol but also to its positive and negative (anti-anxiety) reinforcement potential. The review underscores the advantages of using a developing rat to evaluate alcohol''s motivational effects. [Copyright &y& Elsevier]

Abstract: A large, negative wave which reaches its peak amplitude around 150 ms after stimulus onset, can be found in the Auditory Evoked Potential (AEP) recorded from the lateral amygdala in the rat. Previous studies in our laboratory have repeatedly shown that this N150 component increases during various aversive conditioning protocols and that this increase is attributable to both increases in emotional arousal that are inherent to aversive conditioning and to the formation of an association between the conditioned stimulus (CS) and the aversive unconditioned stimulus (US). Currently it is not known whether the N150 is also enhanced in conditioning procedures with positive reinforcement. To address this issue, we used a Pavlovian conditioning protocol in which an auditory CS signaled the delivery of a food US in food-deprived rats. AEPs evoked by the CS were recorded from the lateral amygdala while the animals were subjected to this appetitive conditioning procedure. Heart rate and N150 amplitude did not increase during conditioning relative to pre-conditioning baselines. In contrast, heart rate and N150 amplitude increases were present during an aversive conditioning protocol (tone–shock pairings) that was carried out after the appetitive conditioning. The present results suggest that the enhancement of the amygdalar N150 is specific for learning experiences that are accompanied by autonomic arousal and that this arousal is a prerequisite for the enhancement of the N150. [Copyright &y& Elsevier]

Abstract: Although the core region of the nucleus accumbens (NAcc) has been implicated in motor control and the acquisition of appetitive learning, these processes are altered by environmental experience. To assess how environment influences neuronal processing in NAcc core, we recorded single-unit activity during acquisition of an appetitive learning task in which rats reared in an environmentally enriched condition (EC) learned the operant response (nosepoke into a lit hole) for sucrose reinforcement faster than rats reared in an isolated condition (IC). In the first training session, even before the emergence of learning differences, core neurons were more likely to respond (increase or decrease activity) during the operant and consummatory responses in EC than IC rats. By the third training session, when learning differences emerged, EC neurons continued to be more responsive than IC neurons, but in very different ways: the response shifted to the cues that signaled trial onset (1900 Hz tone and green LED) and reward availability (4500 Hz tone and yellow LED). Cue-related responding, moreover, was dominated by neuronal excitations. In contrast, post-acquisition recordings revealed no EC-IC differences. Collectively, these results suggest that core neurons are initially more responsive to discrete, goal-directed movements in EC rats, but as learning materializes, the neuronal response shifts to the cues that predict these movements. Thus, environmental experience alters core neuronal processing of both motor- and sensory-related events but at different stages over the course of learning. [Copyright &y& Elsevier]

Methylphenidate (MP) and nicotine would be expected to improve associative learning, though previous evidence suggests that they should reduce the selectivity with which associations are formed. Here we tested their effects on learning the association between a conditioned stimulus (CS) and food (unconditioned stimulus, UCS) in male Wistar rats. The UCS was delivered immediately (0 s) following CS offset or after a 10 s trace. In addition to the measures of discrete CS conditioning, contextual and trace responding was measured in the inter-trial- and the inter-stimulus-interval, respectively. In all cases, conditioning was measured as nose poking for food. Both MP and nicotine improved the acquisition of discrete cue conditioning. Acquisition was accelerated (compared to saline) under 5 but not 1 mg/kg MP and 0.6, but not 0.4 mg/kg nicotine. In each case, this effect was observed in 0 s but not 10 s conditioned groups. For comparison, some earlier published data obtained following the same procedure with D-amphetamine were re-analysed in the same way. Amphetamine similarly improved conditioning in the 0 s group, in this case at 0.5, but not 1.5 mg/kg. Thus three different dopamine agonists increased the ability to focus responding to CS presentations over successive sessions of appetitive acquisition. [ABSTRACT FROM AUTHOR]

Abstract: Anti-epileptic compounds have been linked to several developmental disorders. Specifically, fetal exposure to phenytoin is linked to fetal hydantoin syndrome in humans. We have developed a rat model of fetal hydantoin syndrome in an effort to explore the relationship between drug exposure, development, and learning and memory. Previous studies of this animal model have used various embryological periods of exposure; however, the human syndrome is reported in the offspring of mothers that maintain drug regimens throughout gestation and nursing. To that end, the present study investigated associative learning in rats exposed to therapeutic levels of phenytoin throughout prenatal development and the postnatal pre-weaning period. We used an instrumental appetitive-to-aversive transfer paradigm, which has hippocampal-dependent components, and an avoidance-conditioning paradigm to test simple associative learning and higher-order learning and memory. Compared to controls, we report increased rates of acquisition and performance by the phenytoin group in both the appetitive and the avoidance learning paradigm, and a substantial impairment in avoidance learning following the transfer from appetitive to aversive conditioning. The positive deficit observed with simple associative learning and the negative transfer effect associated with higher order learning suggests that chronic exposure to phenytoin throughout gestation disrupts hippocampal development, which subsequently leads to impaired function in adulthood. [Copyright &y& Elsevier]

Introduction. There is only limited evidence for appetitive classical conditioning of female sexual response, and to date modulation of female sexual response by aversive conditioning has not been studied. Aim. The aim of this article is to study appetitive and aversive classical conditioning of sexual responses in women. Main Outcome Measures. Vaginal pulse amplitude was assessed by vaginal photoplethysmography and ratings of affective value were obtained. Method. Two differential conditioning experiments were conducted. In Experiment 1, on appetitive conditioning, neutral pictures served as conditional stimuli (CSs) and genital vibrotactile stimulation as the unconditional stimulus (US). In Experiment 2, on aversive conditioning, erotic pictures served as CSs and a pain stimulus as US. In both experiments, only one CS (the CS+) was followed by the US during the acquisition phase. Conditioned responses were assessed during the extinction phase. Results. In Experiment 1, during the extinction phase, as expected vaginal pulse amplitude was higher in response to the CS+ than during the CS−. Also, the CS+ was rated as marginally more positive than the CS−. In Experiment 2, during the extinction phase, as expected vaginal pulse amplitude was lower in response to the CS+ than during the CS−, and the CS+ was rated as more negative than the CS−. Conclusions. The results provide evidence for appetitive classical conditioning of sexual response in women, and are the first to show attenuation of sexual response in women by aversive conditioning. Both S, Laan E, Spiering M, Nilsson T, Oomens S, and Everaerd W. Appetitive and aversive classical conditioning of female sexual response. J Sex Med 2008;5:1386–1401. [ABSTRACT FROM AUTHOR]