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The Pavlovian autoshaping paradigm has often been used to assess the behavioral effects of reward omission on behavior. We trained pigeons to receive a food reward (unconditioned stimulus or UCS) following illumination of a response key (conditioned stimulus or CS). In Experiment 1, one group of pigeons was trained with two 100% predictive CS-UCS associations (reward certainty) and another group with two 25% predictive CS-UCS associations (reward uncertainty) for 12 sessions. In both groups, the two CS durations were 8 s. Then, in each group, the duration of one CS remained unchanged and that of the other CS was suddenly extended from 8 to 24 s for 6 sessions. In Experiment 2, some experienced individuals (from Experiment 1) and naïve individuals formed two groups trained with a 24-s CS throughout for 18 sessions. Our results show that pigeons (a) pecked less at the uncertain than the certain CS, (b) decreased and then increased CS-pecking after extending CS duration, especially in the certainty condition, (c) were unresponsive to the 24-s CS in the absence of previous experience, and (d) decreased their response rate close to the end of a trial irrespective of the reinforcement condition, CS duration, and amount of training. These results are discussed in relation to several theoretical frameworks.

The importance of neuronal glutamate to synaptic transmission throughout the brain illustrates the immense therapeutic potential and safety risks of targeting this system. Astrocytes also release glutamate, the clinical relevance of which is unknown as the range of brain functions reliant on signaling from these cells hasn't been fully established. Here, we investigated system xc- (Sxc), which is a glutamate release mechanism with an in vivo rodent expression pattern that is restricted to astrocytes. As most animals do not express Sxc, we first compared the expression and sequence of the obligatory Sxc subunit xCT among major classes of vertebrate species. We found xCT to be ubiquitously expressed and under significant negative selective pressure. Hence, Sxc likely confers important advantages to vertebrate brain function that may promote biological fitness. Next, we assessed brain function in male genetically modified rats (MSxc) created to eliminate Sxc activity. Unlike other glutamatergic mechanisms, eliminating Sxc activity was not lethal and didn't alter growth patterns, telemetry measures of basic health, locomotor activity, or behaviors reliant on simple learning. However, MSxc rats exhibited deficits in tasks used to assess cognitive behavioral control. In a pavlovian conditioned approach, MSxc rats approached a food-predicted cue more frequently than WT rats, even when this response was punished. In attentional set shifting, MSxc rats displayed cognitive inflexibility because of an increased frequency of perseverative errors. MSxc rats also displayed heightened cocaine-primed drug seeking. Hence, a loss of Sxc-activity appears to weaken control over nonreinforced or negative-outcome behaviors without altering basic brain function. [ABSTRACT FROM AUTHOR]

RationaleAdolescence is characterized by endocannabinoid (ECB)-dependent refinement of neural circuits underlying emotion, learning, and motivation. As a result, adolescent cannabinoid receptor stimulation (ACRS) with phytocannabinoids or synthetic agonists like "Spice" cause robust and persistent changes in both behavior and circuit architecture in rodents, including in reward-related regions like medial prefrontal cortex and nucleus accumbens (NAc).Objectives and methodsHere, we examine persistent effects of ACRS with the cannabinoid receptor 1/2 specific agonist WIN55-212,2 (WIN; 1.2 mg/kg/day, postnatal day (PD) 30-43), on natural reward-seeking behaviors and ECB system function in adult male Long Evans rats (PD 60+).ResultsWIN ACRS increased palatable food intake, and altered attribution of incentive salience to food cues in a sign-/goal-tracking paradigm. ACRS also blunted hunger-induced sucrose intake, and resulted in increased anandamide and oleoylethanolamide levels in NAc after acute food restriction not seen in controls. ACRS did not affect food neophobia or locomotor response to a novel environment, but did increase preference for exploring a novel environment.ConclusionsThese results demonstrate that ACRS causes long-term increases in natural reward-seeking behaviors and ECB system function that persist into adulthood, potentially increasing liability to excessive natural reward seeking later in life.

Genome-wide association studies in humans have suggested that variants of the cadherin-13 (CDH13) gene are associated with substance use disorder, subjective response to amphetamine, and attention deficit hyperactivity disorder. To examine the role of the Cdh13 and its peptide ligand adiponectin (AdipoQ) in addiction-related behaviors, we assessed Cdh13 knockout (KO) rats and AdipoQ KO mice using intravenous cocaine self-administration and conditioned place preference (CPP) paradigms. During intravenous cocaine self-administration, male Cdh13 heterozygous (+/-) and KO (-/-) rats showed increased cue-induced reinstatement compared with wild-type (WT) rats when presented with a cocaine-paired stimulus, whereas female Cdh13 rats showed no differences across genotype. Cdh13 -/- rats showed higher responding for a saccharin reinforcer and learned the choice reaction time (RT) task more slowly than WTs. However, we found no differences between Cdh13 -/- and +/+ rats in responding for sensory reinforcement, number of premature responses in the RT task, tendency to approach a Pavlovian food cue, CPP and locomotor activation to cocaine (10 or 20 mg/kg). In AdipoQ -/- mice, there was a significant increase in CPP to methamphetamine (1 mg/kg) but not to a range of d-amphetamine doses (0.5, 1, 2 and 4 mg/kg). Taken together, these data suggest that Cdh13 and AdipoQ regulate sensitivity to psychomotor stimulants and palatable rewards without producing major changes in other behaviors. In humans, these two genes may regulate sensitivity to natural and drug rewards, thus influencing susceptibility to the conditioned drug effects and relapse.

The Price equation is a mathematical expression of selectionist and non-selectionist pressures on biological, cultural, and behavioral change. We use it here to specify instrumental and noninstrumental behaviors as they arise within the context of the Pavlovian autoshaping procedure, for rats trained under reward certainty and reward uncertainty. The point of departure for this endeavor is that some portion of autoshaped behavior referred to as goal-tracking appears instrumental—a function of resource attainment (the individual approaches the location where the unconditioned stimulus is to be delivered). By contrast, some other portion of autoshaped behavior referred to as sign-tracking is noninstrumental—irrelevant to making contact with the to-be-delivered unconditioned stimulus. A Price equation model is proposed that unifies our understanding of Pavlovian autoshaping behavior by isolating operant and respondent influences on goal-tracking (instrumental) and sign-tracking (noninstrumental) behavior. [ABSTRACT FROM AUTHOR]

RationaleDisorders of behavioral regulation, including attention deficit hyperactivity disorder (ADHD) and drug addiction, are in part due to poor inhibitory control, attentional deficits, and hyper-responsivity to reward-associated cues.ObjectivesTo determine whether these traits are related, we tested genetically variable male and female heterogeneous stock rats in the choice reaction time (CRT) task and Pavlovian conditioned approach (PavCA). Sex differences in the response to methylphenidate during the CRT were also assessed.MethodsIn the CRT task, rats were required to withhold responding until one of two lights indicated whether responses into a left or right port would be reinforced with water. Reaction time on correct trials and premature responses were the operational definitions of attention and response inhibition, respectively. Rats were also pretreated with oral methylphenidate (0, 2, 4 mg/kg) during the CRT task to determine whether this drug would improve performance. Subsequently, during PavCA, presentation of an illuminated lever predicted the delivery of a food pellet into a food-cup. Lever-directed approach (sign-tracking) and food-cup approach (goal-tracking) were the primary measures, and rats were categorized as "sign-trackers" and "goal-trackers" using an index based on these measures.ResultsSign-trackers made more premature responses than goal-trackers but showed no differences in reaction time. There were sex differences in both tasks, with females having higher sign-tracking, completing more CRT trials, and making more premature responses after methylphenidate administration.ConclusionsThese results indicate that response inhibition is related to reward-cue responsivity, suggesting that these traits are influenced by common genetic factors.

The endocannabinoid system is responsible for regulating a spectrum of physiological activities and plays a critical role in the developing brain. During adolescence, the endocannabinoid system is particularly sensitive to external insults that may change the brain’s developmental trajectory. Cannabinoid receptor type 2 (CB2R) was initially thought to predominantly function in the peripheral nervous system, but more recent studies have implicated its role in the mesolimbic pathway, a network largely attributed to reward circuitry and reward motivated behavior, which undergoes extensive changes during adolescence. It is therefore important to understand how CB2R modulation during adolescence can impact reward-related behaviors in adulthood. In this study, adolescent male rats (postnatal days 28–41) were exposed to a low or high dose of the CB2R antagonist/inverse agonist SR144528 and Pavlovian autoshaping and instrumental conditional behavioral outcomes were measured in adulthood. SR144528-treated rats had significantly slower acquisition of the autoshaping task, seen by less lever pressing behavior over time [F(2, 19) = 5.964, p = 0.010]. Conversely, there was no effect of adolescent SR144528 exposure on instrumental conditioning. These results suggest that modulation of the CB2R in adolescence differentially impacts reward-learning behaviors in adulthood.

Animals appoint incentive value and learn to approach otherwise behaviorally inert stimuli if these stimuli come to predict the delivery of reward. Interestingly, this adaptive Pavlovian learning process has been implicated in behavioral control disorders, such as drug addiction. One brain region implicated in directing conditioned approach behavior is the prelimbic region of the prefrontal cortex. The present study employed in vivo electrophysiology in the prelimbic cortex to characterize the distribution of neural responses to the presence of a cue that had acquired incentive value after being associated with a primary reward. Male rats were trained in a Pavlovian autoshaping task in which a lever was presented prior to reward delivery. Following repeated pairings of lever availability and reward delivery, rats pressed the lever even though reward delivery was not contingent on any interaction with the lever. Neurons in the prelimbic cortex selectively encoded the presentation of the reward‐predicting lever. Although the response was heterogeneous, most responsive neurons decreased their firing rate in response to the presence of the lever. These findings characterize the varied responses of prelimbic cortical neurons to reward cues and are consistent with evidence that the role of the prelimbic cortex in reward learning depends on the downstream target. [ABSTRACT FROM AUTHOR]

We examined the role of the avian hippocampus and area parahippocampalis in serial‐order behavior and a variety of other tasks known to be sensitive to hippocampal damage in mammals. Damage to the hippocampus and area parahippocampalis caused impairments in autoshaping and performance on an analogue of a radial‐arm maze task, but had no effect on acquisition of 2‐item, 3‐item, and 4‐item serial‐order lists. Additionally, the lesions had no effect on the retention of 3‐items lists, or on the ability to perform novel derived lists composed of elements from lists they had previously learned. The impairments in autoshaping and spatial behavior are consistent with the findings in mammals. The absence of impairments on the serial‐order task may also be consistent once one considers that damage to the hippocampus in mammals seems to affect more internally‐organized rather than externally‐organized serial‐order tasks. Together, the findings support the view that the avian hippocampal complex serves a function very similar to the mammalian hippocampus, a finding that is interesting given that the architecture of the avian hippocampus differs dramatically from that of the mammalian hippocampus. [ABSTRACT FROM AUTHOR]

Introduction and goal: Learning and motivational processes have been central for a modern understanding of tobacco addiction. There is evidence that supports the importance of incentive motivational processes for the maintenance of tobacco addiction. The main goal of the present experiment was to evaluate the effects of acute nicotine on the incentive value of a natural reward, (food) paired with an environmental cue (pressing lever). Method: Wistar rats were used. Accute nicotine (0.4 mg/kg) was administered on key sessions, using a pavlovian autoshaping procedure involving ten acquisition and four extinction sessions. The experimental design included three groups, a saline administration control group and groups with specific nicotine administration during either acquisition or extinction. Results: We found that acute administration of nicotine, in contrast with saline only or previous nicotine administration during acquisition, had an enhancing effect on responding for the environmental cue during autoshaping extinction, but we did not find evidence that acute nicotine affected acquisition performance. Conclusion: Our results are consistent with a role of nicotine enhancing the incentive value of stimuli during extinction from a pavlovian autoshaping task. [ABSTRACT FROM AUTHOR]

The Pavlovian autoshaping paradigm has often been used to assess the behavioral effects of reward omission on behavior. We trained pigeons to receive a food reward (unconditioned stimulus, or UCS) following illumination of a response key (conditioned stimulus, or CS). In Experiment 1, 1 group of pigeons was trained with two 100% predictive CS-UCS associations (reward certainty) and another group with two 25% predictive CS-UCS associations (reward uncertainty) for 12 sessions. In both groups, the 2 CS durations were 8 s. Then, in each group, the duration of 1 CS remained unchanged and that of the other CS was suddenly extended from 8 to 24 s for 6 sessions. In Experiment 2, some experienced individuals (from Experiment 1) and naïve individuals formed 2 groups trained with a 24-s CS throughout for 18 sessions. Our results show that pigeons (a) pecked less at the uncertain than the certain CS, (b) decreased and then increased CS-pecking after extending the CS duration, especially in the certainty condition, (c) were unresponsive to the 24- s CS in the absence of previous experience, and (d) decreased their response rate close to the end of a trial irrespective of the reinforcement condition, CS duration, and amount of training. These results are discussed in relation to several theoretical frameworks. [ABSTRACT FROM AUTHOR]

Cue competition refers to phenomena indicating that learning about the relationship between a cue and an outcome is influenced by learning about the predictive significance of other cues that are concurrently present. In two autoshaping experiments with pigeons, we investigated the strength of competition among cues for predictive value. In each experiment, animals received an overexpectation training (A+, D+ followed by AD+). In addition, the training schedule of each experiment comprised two control conditions—one condition to evaluate the presence of overexpectation (B+ followed by BY+) and a second one to assess the strength of competition among cues (C+ followed by CZ−). Training trials were followed by a test with individual stimuli (A, B, C). Experiment 1 revealed no evidence for cue competition as responding during the test mirrored the individual cue–outcome contingencies. The test results from Experiment 2, which included an outcome additivity training, showed cue competition in form of an overexpectation effect as responding was weaker for Stimulus A than Stimulus B. However, the test results from Experiment 2 also revealed that responding to Stimulus A was stronger than to Stimulus C, which indicates that competition among cues was not as strong as predicted by some influential theories of associative learning. [ABSTRACT FROM AUTHOR]

Reward uncertainty is a common characteristic of gambling and may powerfully enhance attraction to gambling-related cues, thus promoting maladaptive gambling behaviors in susceptible individuals. The co-occurrence of gambling disorder with tobacco use disorder (60.4%) suggests a common mechanism for their pathology, and comorbid anxiety (41.3%) might further promote the maintenance of these behaviors. However, it is unknown how nicotine or anxiety might contribute to cue and reward attraction, or promote disordered gambling behavior. In the present study, we investigated the effects of nicotine (0.4 mg/kg, SC) on the desire for uncertain rewards and their cues in male and female Sprague-Dawley rats. During an autoshaping task, rats learned to associate a lever + tone cue with the delivery of sucrose pellet rewards under either certain or uncertain (probability and magnitude) reward conditions. Subsequently, we tested the ability of gambling-like cues to serve as a conditioned reinforcer, and to promote motivation for sucrose rewards during a progressive ratio task. Finally, anxiety behavior was measured to examine its interaction with nicotine and uncertainty. Here, we found that nicotine enhanced attraction to the magazine under certain but not uncertain reward conditions, and increased cue-triggered behaviors. Conversely, in the progressive ratio task, exposure to uncertain conditions and nicotine enhanced motivation for reward, compared with certain conditions. These results suggest that nicotine may interact with both certain and uncertain reward conditions to increase cue-triggered behavior and enhance motivation for rewards, providing possible insight into the comorbid relationship between pathological gambling and tobacco use. [ABSTRACT FROM AUTHOR]

Background: Nicotine and alcohol use are highly comorbid. Modulation of drug‐paired extrinsic and intrinsic cues likely plays a role in this interaction, as cues can acquire motivational properties and augment drug seeking. The motivational properties of cues can be measured through Pavlovian conditioning paradigms, in which cues either elicit approach following pairing with the reinforcing properties of alcohol or elicit avoidance following pairing with the aversive consequences of alcohol. The present experiments tested whether nicotine would enhance the incentive properties of an appetitive ethanol (EtOH) cue and diminish the avoidance of an aversive EtOH cue in Pavlovian paradigms. Methods: In experiment 1, male Long‐Evans rats with or without prior chronic intermittent access to EtOH were administered nicotine or saline injections prior to Pavlovian conditioned approach (PavCA) sessions, during which conditioned approach to the cue ("sign‐tracking") or the EtOH delivery location ("goal‐tracking") was measured. In experiment 2, male Long‐Evans rats were administered nicotine or saline injections prior to pairing a flavor cue with increasing doses of EtOH (i.p.) in an adaptation of the conditioned taste avoidance (CTA) paradigm. Results: Results from PavCA indicate that, regardless of EtOH exposure, nicotine enhanced responding elicited by EtOH‐paired cues with no effect on a similar cue not explicitly paired with EtOH. Furthermore, nicotine reduced sensitivity to EtOH‐induced CTA, as indicated by a rightward shift in the dose–response curve of passively administered EtOH. The ED50, or the dose of EtOH that produced a 50% reduction in intake relative to baseline, was significantly higher in nicotine‐treated rats compared to saline‐treated rats. Conclusions: We conclude that nicotine increases the approach and diminishes the avoidance elicited by Pavlovian cues paired, respectively, with the reinforcing and aversive properties of EtOH consumption in male rats. As such, nicotine may enhance alcoholism liability by engendering an attentional bias toward cues that predict the reinforcing outcomes of drinking. [ABSTRACT FROM AUTHOR]

The orbitofrontal cortex (OFC) is critical for updating reward-directed behaviours flexibly when outcomes are devalued or when task contingencies are reversed. Failure to update behaviour in outcome devaluation and reversal learning procedures are considered canonical deficits following OFC lesions in non-human primates and rodents. We examined the generality of these findings in rodents using lesions of the rodent lateral OFC (LO) in instrumental action-outcome and Pavlovian cue-outcome devaluation procedures. LO lesions disrupted outcome devaluation in Pavlovian but not instrumental procedures. Furthermore, although both anterior and posterior LO lesions disrupted Pavlovian outcome devaluation, only posterior LO lesions were found to disrupt reversal learning. Posterior but not anterior LO lesions were also found to disrupt the attribution of motivational value to Pavlovian cues in sign-tracking. These novel dissociable task- and subregion-specific effects suggest a way to reconcile contradictory findings between rodent and non-human primate OFC research.

Following repeated pairings, the reinforcing and motivational properties (incentive salience) of a reward can be transferred onto an environmental stimulus which can then elicit conditioned responses, including Pavlovian approach behavior to the stimulus (a sign-tracking response). In rodents, acquisition of sign-tracking in autoshaping paradigms is sensitive to lesions and dopamine D1 receptor antagonism of the nucleus accumbens (NAc) of the ventral striatum. However, currently, the possible roles of dorsal striatal subregions, as well as of the two major striatal neuron types, dopamine D1-/D2-expressing medium spiny neurons (MSNs), in controlling the development of conditioned responses is still unclear and warrants further study. Here, for the first time, we used a transgenic mouse line combined with striatal subregion-specific AAV virus injections to separately express tetanus toxin in D1-/D2- MSNs in the NAc, dorsomedial striatum, and dorsolateral striatum, to permanently block neurotransmission in these neurons during acquisition of an autoshaping task. Neurotransmission blocking of NAc D1-MSNs inhibited the acquisition of sign-tracking responses when the initial conditioned response for each conditioned stimulus presentation was examined, confirming our initial hypothesis. These findings suggest that activity in NAc D1-MSNs contributes to the attribution of incentive salience to conditioned stimuli.

Highlights • Serotonergic 5-HT 6 receptor tone on memory and/or amnesia. • Dose-response curves of 5-HT 6 receptor experimental molecules. • Different intrinsic activity. • Hippocampal serotonergic tone under amnesic states. Abstract To our knowledge the intrahippocampal serotonergic 5-HT 6 receptor tone on memory and amnesia models remains unexplored. Hence, in the present work we tested intrahippocampal administration of serotonin or 5-hydroxytryptamine (5-HT) 6 receptor experimental molecules with differential intrinsic activity. Methods: In the present study, Automatized Autoshaping memory task was used, useful measuring memory, neural markers, and pharmacological effects. We are hypothesizing that experimental molecules with differential intrinsic activity might reveal serotonergic tone. Particularly, intrahippocampal administration of 5-HT 6 receptor compounds with differential intrinsic activity (i.e., agonistic and antagonistic) might evidencing a serotonergic tone via this receptor. Bilateral intrahippocampal dose-response curves show that administration of EMD386088 (10 and 100 μg) had no effect or (50 μg) decreased conditioned responses (CR) in short- and long-term memory (STM and LTM, respectively); while SB-399885 (10 or 100 μg) significantly decreased CR in STM and LTM (24 and 48-h) or (50 μg) had no effect; thus suggesting that there is a 5-HT 6 receptor tone regulating both STM and LTM. Moreover, intrahippocampal inactive doses of EMD386088 (5 μg) plus SB-399885 (0.5 μg) did not affect STM and LTM; however, partially or completely prevented the scopolamine or dizocilpine-induced amnesia. Thus confirming that both drugs exerted their effects through 5-HT 6 receptor and that there is a hippocampal serotonergic tone under amnesic states, similar to that striatal. [ABSTRACT FROM AUTHOR]

Alcohol use disorder commonly occurs in patients with schizophrenia and contributes greatly to its morbidity. Unfortunately, the neural and behavioral underpinnings of alcohol drinking in these patients are not well understood. In order to begin to understand the cognitive and reward-related changes that may contribute to alcohol drinking, this study was designed to address: 1) latent inhibition; 2) conditioning; and 3) extinction of autoshaping in a neurodevelopmental rat model with relevance to co-occurring schizophrenia and alcohol use disorders, the neonatal ventral hippocampal lesioned (NVHL) rat. NVHL lesions (or sham surgeries) were performed on post-natal day 7 (PND7) and animals were given brief exposure to alcohol during adolescent (PND 28-42). Latent inhibition of autoshaping, conditioning and extinction were assessed between PND 72-90. On PND90 animals were given alcohol again and allowed to establish stable drinking. Latent inhibition of autoshaping was found to be prolonged in the NVHL rats; the NVHL rats pre-exposed to the lever stimulus were slower to acquire autoshaping than sham pre-exposed rats. NVHL rats that were not pre-exposed to the lever stimulus did not differ during conditioning, but were slower to extinguish conditioned responding compared to sham controls. Finally, the NVHL rats from both groups drank significantly more alcohol than sham rats, and the extent of latent inhibition predicted future alcohol intake in the pre-exposed animals. These findings suggest that the latent inhibition of autoshaping procedure can be used to model cognitive- and reward-related dysfunctions in schizophrenia, and these dysfunctions may contribute to the development of co-occurring alcohol use. [ABSTRACT FROM AUTHOR]

Pavlovian conditioning is evident in every species in which it has been assessed, and there is a consensus about its interpretation across behavioral, 1,2 brain, 3,4,5,6 and computational analyses 7,8,9,10,11 : conditioned behavior reflects the formation of a directional associative link from the memory of one stimulus (e.g., a visual stimulus) to another (e.g., food), with learning stopping when there is no error between the prediction generated by the visual stimulus and what happens next (e.g., food). This consensus fails to anticipate the results that we report here. In our experiments with rats, we find that arranging predictive (visual stimulus→food) and nonpredictive (food→visual stimulus) relationships produces marked and sustained changes in conditioned behaviors when the visual stimulus is presented alone. Moreover, the type of relationship affects (1) the distribution of conditioned behaviors related to the properties of both food (called goal-tracking) and the visual stimulus (called sign-tracking) and (2) when in the visual stimulus, these two behaviors are evident. These results represent an impetus for a fundamental shift in how Pavlovian conditioning is interpreted: animals learn about the relationship between two stimuli irrespective of the order in which they are presented, but they exhibit this knowledge in different ways. This interpretation and our new results are captured by a recent model of Pavlovian conditioning, 12,13 HeiDI, and both are consistent with the need for animals to represent the fact that the impact of a cause (e.g., the ingestion of nutrients or the bite of a predator) can be felt before or after the cause has been perceived. • The impact of predictive and nonpredictive relationships was assessed in rats • Both relationships generated conditioned responding • However, the nature and timing of responding was affected by these relationships • The results are predicted by a recent model of associative learning, HeiDI Navarro et al. study the impact of predictive and nonpredictive relationships on conditioned responding in rats. The results contradict standard models of conditioning, which emphasize predictive relationships, but are predicted by the HeiDI model, which assumes that both relationships generate reciprocal associations that support responding. [ABSTRACT FROM AUTHOR]

Rewarding doses of amphetamine increase the amplitude, duration, and frequency of dopamine transients in the ventral striatum. Debate continues at the behavioral level about which component of reward, learning or incentive salience, is signaled by these dopamine transients and thus altered in addiction. The learning hypothesis proposes that rewarding drugs result in pathological overlearning of drug-predictive cues, while the incentive sensitization hypothesis suggests that rewarding drugs result in sensitized attribution of incentive salience to drug-predictive cues. Therapeutic doses of amphetamine, such as those used to treat attention-deficit hyperactivity disorder, are hypothesized to enhance the ventral striatal dopamine transients that are critical for reward-related learning and to enhance Pavlovian learning. However, the effects of therapeutic doses of amphetamine on Pavlovian learning are poorly understood, and the effects on dopamine transients are completely unknown. We determined the effects of an acute pre-training therapeutic or rewarding amphetamine injection on the acquisition of Pavlovian autoshaping in the intact rat. We also determined the effects of these doses on electrically evoked transient-like dopamine signals using fast-scan cyclic voltammetry in the anesthetized rat. The rewarding dose enhanced the amplitude and duration of DA signals, caused acute task disengagement, impaired learning for several days, and triggered incentive sensitization. The therapeutic dose produced smaller enhancements in DA signals but did not have similar behavioral effects. These results underscore the necessity of more studies using therapeutic doses, and suggest a hybrid learning/incentive sensitization model may be required to explain the development of addiction. [ABSTRACT FROM AUTHOR]

An autoshaping procedure was used to test the notion that conditioned stimuli (CSs) gain greater incentive salience during adolescence than young adulthood under conditions of social isolation rearing and food restriction. Rats were single-housed and placed on food restriction during 10 daily training sessions in which a lever (CS+) was presented then followed immediately by a food unconditioned stimulus (US). A second lever (CS−) was presented on intermixed trials and was not reinforced. Despite the fact that food delivery was not contingent on the rats' behavior, all rats exhibited behaviors directed towards the lever (i.e., sign-tracking). In the adolescent group, the rate of lever pressing and the percentage of trials with a lever press were higher than in young adults. Initially, group differences were observed when rats were retrained when the adolescents had reached young adulthood. These findings support the hypothesis that cues that come to predict reward become imbued with excessive motivational value in adolescents, perhaps contributing to the hyper-responsiveness to reward-related stimuli typically observed during this period of development. [ABSTRACT FROM AUTHOR]

The neural circuitry underlying behavior in reward loss situations is poorly understood. We considered two such situations: reward devaluation (from large to small rewards) and reward omission (from large rewards to no rewards). There is evidence that the central nucleus of the amygdala (CeA) plays a role in the negative emotion accompanying reward loss. However, little is known about the function of the basolateral nucleus (BLA) in reward loss. Two hypotheses of BLA function in reward loss, negative emotion and reward comparisons, were tested in an experiment involving pretraining excitotoxic BLA lesions followed by training in four tasks: consummatory successive negative contrast (cSNC), autoshaping (AS) acquisition and extinction, anticipatory negative contrast (ANC), and open field testing (OF). Cell counts in the BLA (but not in the CeA) were significantly lower in animals with lesions vs. shams. BLA lesions eliminated cSNC and ANC, and accelerated extinction of lever pressing in AS. BLA lesions had no effect on OF testing: higher activity in the periphery than in the central area. This pattern of results provides support for the hypothesis that BLA neurons are important for reward comparison. The three affected tasks (cSNC, ANC, and AS extinction) involve reward comparisons. However, ANC does not seem to involve negative emotions and it was affected, whereas OF activity is known to involve negative emotion, but it was not affected. It is hypothesized that a circuit involving the thalamus, insular cortex, and BLA is critically involved in the mechanism comparing current and expected rewards. [ABSTRACT FROM AUTHOR]

Environmental stimuli that are reliably paired with alcohol may acquire incentive salience, a property that can operate in the use and abuse of alcohol. Here we investigated the incentive salience of Pavlovian alcohol cues using a preclinical animal model. Male, Long-Evans rats (Harlan) with unrestricted access to food and water were acclimated to drinking 15% ethanol (v/v) in their home-cages. Rats then received Pavlovian autoshaping training in which the 10 second presentation of a retractable lever served as the conditioned stimulus (CS) and 15% ethanol served as the unconditioned stimulus (US) (0.2 ml/CS; 12 CS presentations/session; 27 sessions). Next, in an operant test of conditioned reinforcement, nose pokes into an active aperture delivered presentations of the lever-CS, whereas nose pokes into an inactive aperture had no consequences. Across initial autoshaping sessions, goal-tracking behavior, as measured by entries into the fluid port where ethanol was delivered, developed rapidly. However, with extended training goal-tracking diminished, and sign-tracking responses, as measured by lever-CS activations, emerged. Control rats that received explicitly unpaired CS and US presentations did not show goal-tracking or sign-tracking responses. In the test for conditioned reinforcement, rats with CS-US pairings during autoshaping training made more active relative to inactive nose pokes, whereas rats in the unpaired control group did not. Moreover, active nose pokes were positively correlated with sign-tracking behavior during autoshaping. Extended training may produce a shift in the learned properties of Pavlovian alcohol cues, such that after initially predicting alcohol availability they acquire robust incentive salience.

Autoshaping is a Pavlovian learning paradigm in which rats experience pairings of a CS and a US independently of their behavior. When the CS is a lever inserted into the test cage and the US is food delivered to an adjacent magazine, many rats acquire a lever-pressing response called ‘sign-tracking’ even though that response has no effect on the occurrence of either the CS or the US. Since these lever presses are always followed by the US, it has been suggested that sign-tracking could be due to unintended reinforcement of the response. To eliminate the possibility of such instrumental learning the omission schedule, in which a response to the CS cancels the US, was introduced. Previous research has shown that training rats on autoshaping and switching them to an omission schedule generally reduces but does not eliminate sign-tracking, suggesting that it may be due to both Pavlovian and instrumental learning. In the present study naive rats trained on an omission schedule sign-tracked less than a control group exposed to random, unpaired CS and US presentations, suggesting that they learned to withhold the lever press response because of the negative contingency between that response and the US. In a second experiment rats with dorsal hippocampus lesions sign-tracked more than sham-lesioned rats on omission schedules, suggesting that this case of learning not to respond is hippocampus-based. This conclusion is consistent with many previous findings on the inability of hippocampal rats to withhold or suppress responding, and with studies suggesting that one form of extinction of learned responses in normal rats is due to competition from hippocampus-based learning not to respond. [ABSTRACT FROM AUTHOR]

Rationale: Individuals prone to attribute incentive salience to food-associated stimuli ('cues') are also more sensitive to cues during drug seeking and drug taking. This may be due in part to a difference in sensitivity to the affective or other stimulus properties of the drug. In rats, these properties are associated with 50-kHz ultrasonic vocalizations (USVs), in that they are elicited during putative positive affective and motivational states, including in response to drugs of abuse. Objectives: We sought to determine whether individual differences in the tendency to attribute incentive salience to a food cue (as measured by approach) were associated with differences in cocaine-induced USVs. We also tested whether the food cue would elicit USVs and if this response was related to approach to the food cue. Methods: In experiment 1, rats underwent Pavlovian conditioned approach (PavCA) training where they learned to associate a cue (an illuminated lever) with the delivery of a food pellet into a food cup. Subjects were categorized based on their approach to the cue ('sign-trackers') or to the food cup ('goal-trackers'). Rats subsequently underwent nine testing days in which they were given saline or cocaine (10 mg/kg i.p) and placed into a locomotor chamber. In experiment 2, rats were first tested in the locomotor chambers for one saline-treated day followed by one cocaine-treated day and then trained in PavCA. USVs were recorded from a subset of individuals during the last day of PavCA to determine if the food cue would elicit USVs. Results: Sign-trackers produced 5-24 times more cocaine-induced 50 kHz USVs compared to goal-trackers for all days of experiment 1, and this response sensitized with repeated cocaine, only in sign-trackers. Similarly in experiment 2, individuals that produced the most cocaine-induced USVs on a single exposure also showed the greatest tendency to sign-track during PavCA. Lastly, while sign-trackers produced more USVs during PavCA generally, the cue itself did not elicit additional USVs in sign- or goal-trackers. Conclusions: These results indicate a robust and consistent relationship between approach to a food cue and cocaine-induced USV production. Thus, these USVs may index the neurobiological differences underlying the behavioral distinctions of sign- and goal-trackers. [ABSTRACT FROM AUTHOR]

Individual differences exist in the attribution of incentive salience to conditioned stimuli associated with food. Here, we investigated whether individual differences also manifested with a Pavlovian alcohol conditioned stimulus (CS). We compiled data from five experiments that used a Pavlovian autoshaping paradigm and tests of conditioned reinforcement. In all experiments, male, Long-Evans rats with unrestricted access to food and water were acclimated to 15% ethanol. Next, rats received Pavlovian autoshaping training, in which a 10 s presentation of a retractable lever served as the CS and 0.2 mL of 15% ethanol served as the unconditioned stimulus (US). Finally, rats underwent conditioned reinforcement tests in which nose-pokes to an active aperture led to brief presentations of the lever-CS, but nose-pokes to an inactive aperture had no consequence. Rats were categorized as sign-trackers, goal-trackers and intermediates based on a response bias score that reflected their tendencies to sign-track or goal-track at different times during training. We found that distinct groups of rats either consistently interacted with the lever-CS ("sign-trackers") or routinely approached the port during the lever-CS ("goal-trackers") across a majority of the training sessions. However, some individuals ("shifted sign-trackers") with an early tendency to goal-track later shifted to comparable asymptotic levels of sign-tracking as the group identified as sign-trackers. The lever-CS functioned as a conditioned reinforcer for sign-trackers and shifted sign-trackers, but not for goal-trackers. These results provide evidence of robust individual differences in the extent to which a Pavlovian alcohol cue gains incentive salience and functions as a conditioned reinforcer . [ABSTRACT FROM AUTHOR]

ABSTRACT Individual variation in the attribution of motivational salience to reward-related cues is believed to underlie addiction vulnerability. Pavlovian conditioned approach measures individual variation in motivational salience by identifying rats that are attracted to and motivated by reward cues (sign-trackers) or motivationally fixed on the reward itself (goal-trackers). Previously, it has been demonstrated that sign-trackers are more vulnerable to addiction-like behavior. Moreover, sign-trackers release more dopamine in the nucleus accumbens than goal-trackers in response to reward-related cues, and sign- but not goal-tracking behavior is dopamine-dependent. In the present study, we investigated whether the ventral hippocampus, a potent driver of dopaminergic activity in the nucleus accumbens, modulates the acquisition and expression of Pavlovian conditioned approach behavior. In Experiment 1, lesions of the ventral, but not dorsal or total hippocampus, decreased sign-tracking behavior. In Experiment 2, lesions of the ventral hippocampus did not affect the expression of sign- or goal-tracking behaviors nor conditioned reinforcement. In addition, temporary inactivation of the ventral subiculum, the main output pathway of the ventral hippocampus, did not affect the expression of sign- or goal-tracking behaviors. High-pressure liquid chromatography of nucleus accumbens tissue punches revealed that ventral hippocampal lesions decreased levels of homovanillic acid and the homovanillic acid/dopamine ratio (a marker of dopamine release and metabolism) in only sign-trackers, and decreased accumbal norepinephrine levels in both sign- and goal-trackers. These results suggest that the ventral hippocampus is important for the acquisition but not expression of sign-tracking behavior, possibly as a result of altered dopamine and norepinephrine in the nucleus accumbens. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The power of drug-associated cues to instigate drug ‘wanting’ and consequently promote drug seeking is a corner stone of contemporary theories of addiction. Gambling disorder has recently been added to the pantheon of addictive disorders due to the phenomenological similarities between the diseases. However, the neurobiological mechanism that may mediate increased sensitivity towards conditioned stimuli in addictive disorders is unclear. We have previously demonstrated using a rodent analogue of a simple slot machine that the dopamine D 4 receptor is critically engaged in controlling animals’ attribution of salience to stimuli associated with reward in this paradigm, and consequently may represent a target for the treatment of gambling disorder. Here, we investigated the role of acute administration of a D 4 receptor agonist on animals’ responsivity to conditioned stimuli on both a Pavlovian conditioned approach (autoshaping) and a conditioned reinforcement paradigm. Following training on one of the two tasks, separate cohorts of rats (male and female) were administered a dose of PD168077 shown to be maximally effective at precipitating errors in reward expectancy on the rat slot machine task (10 mg/kg). However, augmenting the activity of the D 4 receptors in this manner did not alter behaviour on either task. These data therefore provide novel evidence that the D 4 receptor does not alter incentive motivation in response to cues on simple behavioural tasks. [ABSTRACT FROM AUTHOR]

Rationale: Some individuals are particularly responsive to reward-associated stimuli ('cues'), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. Objectives: To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food-predictive cue ('sign-trackers') or a reward-delivery location ('goal-trackers'). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. Methods: Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue-induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. Results: Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. Conclusions: Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs. [ABSTRACT FROM AUTHOR]

Pavlovian cues for rewards can become attractive incentives: approached and 'wanted' as the rewards themselves. The motivational attractiveness of a previously learned cue is not fixed, but can be dynamically amplified during re-encounter by simultaneous activation of brain limbic circuitry. Here it was reported that opioid or dopamine microinjections in the dorsolateral quadrant of the neostriatum ( DLS) of rats selectively amplify attraction toward a previously learned Pavlovian cue in an individualized fashion, at the expense of a competing cue. In an autoshaping (sign-tracking vs. goal-tracking) paradigm, microinjection of the mu opioid receptor agonist ( DAMGO) or dopamine indirect agonist (amphetamine) in the DLS of sign-tracker individuals selectively enhanced their sign-tracking attraction toward the reward-predictive lever cue. By contrast, DAMGO or amphetamine in the DLS of goal-trackers selectively enhanced prepotent attraction toward the reward-proximal cue of sucrose dish. Amphetamine also enhanced goal-tracking in some sign-tracker individuals (if they ever defected to the dish even once). That DLS enhancement of cue attraction was due to stronger motivation, not stronger habits, was suggested by: (i) sign-trackers flexibly followed their cue to a new location when the lever was suddenly moved after DLS DAMGO microinjection; and (ii) DAMGO in the DLS also made sign-trackers work harder on a new instrumental nose-poke response required to earn presentations of their Pavlovian lever cue (instrumental conditioned reinforcement). Altogether, the current results suggest that DLS circuitry can enhance the incentive salience of a Pavlovian reward cue, selectively making that cue a stronger motivational magnet. [ABSTRACT FROM AUTHOR]

Rationale: The expression of sign-tracking (ST) phenotype over goal-tracking (GT) phenotype has been associated to different aspects of impulsive behavior, and depletions of brain serotonin (5-HT) have been shown to selectively increase impulsive action as well as ST. Objectives: The present study aimed at testing the relationship between reduced brain 5-HT availability and expression of ST phenotype in a genetic model of individual variation in brain 5-HT functionality. Inbred DBA/2J (DBA) mice are homozygous for the allelic variant of the TPH-2 gene causing lower brain 5-HT function in comparison with C57BL/6J (C57) inbred mice. Materials: Young adult (10 weeks) and adult (14 weeks) C57 and DBA mice were trained in a Pavlovian conditioned approach (PCA) paradigm. Lever-directed (ST) and magazine-directed (GT) responses were measured in 12 daily conditioning sessions. In a second experiment, effect of the medial prefrontal cortex (mPFC) 5-HT depletion by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) was assessed on acquisition of ST phenotype in adult C57 mice, according to their higher 5-HT functionality compared to DBA mice. Results: Young adult mice of both strains developed ST phenotype, but only adult DBA mice developed ST phenotype. 5-HT depletion in the mPFC of adult C57 mice completely changed their phenotype, as shown by their increased ST. Conclusions: These findings indicate that ST phenotype can be the expression of a transitory late developmental stage and that genetic factors determine persistence of this phenotype in adulthood. These findings also support a role of 5-HT transmission in PFC in constraining development of ST phenotype. [ABSTRACT FROM AUTHOR]

Environmental stimuli that are reliably paired with alcohol may acquire incentive salience, a property that can operate in the use and abuse of alcohol. Here we investigated the incentive salience of Pavlovian alcohol cues using a preclinical animal model. Male, Long-Evans rats (Harlan) with unrestricted access to food and water were acclimated to drinking 15% ethanol (v/v) in their home-cages. Rats then received Pavlovian autoshaping training in which the 10 s presentation of a retractable lever served as the conditioned stimulus (CS) and 15% ethanol served as the unconditioned stimulus (US) (0.2 ml/CS; 12 CS presentations/session; 27 sessions). Next, in an operant test of conditioned reinforcement, nose pokes into an active aperture delivered presentations of the lever-CS, whereas nose pokes into an inactive aperture had no consequences. Across initial autoshaping sessions, goal-tracking behavior, as measured by entries into the fluid port where ethanol was delivered, developed rapidly. However, with extended training goal-tracking diminished, and sign-tracking responses, as measured by lever- CS activations, emerged. Control rats that received explicitly unpaired CS and US presentations did not show goal-tracking or sign-tracking responses. In the test for conditioned reinforcement, rats with CS-US pairings during autoshaping training made more active relative to inactive nose pokes, whereas rats in the unpaired control group did not. Moreover, active nose pokes were positively correlated with sign-tracking behavior during autoshaping. Extended training may produce a shift in the learned properties of Pavlovian alcohol cues, such that after initially predicting alcohol availability they acquire robust incentive salience. [ABSTRACT FROM AUTHOR]

Gaining a better understanding of the biological mechanisms underlying the individual variation observed in response to rewards and reward cues could help to identify and treat individuals more prone to disorders of impulsive control, such as addiction. Variation in response to reward cues is captured in rats undergoing autoshaping experiments where the appearance of a lever precedes food delivery. Although no response is required for food to be delivered, some rats (goal-trackers) learn to approach and avidly engage the magazine until food delivery, whereas other rats (sign-trackers) come to approach and engage avidly the lever. The impulsive and often maladaptive characteristics of the latter response are reminiscent of addictive behaviour in humans. In a previous article, we developed a computational model accounting for a set of experimental data regarding sign-trackers and goal-trackers. Here we show new simulations of the model to draw experimental predictions that could help further validate or refute the model. In particular, we apply the model to new experimental protocols such as injecting flupentixol locally into the core of the nucleus accumbens rather than systemically, and lesioning of the core of the nucleus accumbens before or after conditioning. In addition, we discuss the possibility of removing the food magazine during the inter-trial interval. The predictions from this revised model will help us better understand the role of different brain regions in the behaviours expressed by sign-trackers and goal-trackers. [ABSTRACT FROM AUTHOR]

Rationale: The serotonin (5-hydroxytryptamine (5-HT)) 5-HT receptor is localized in brain areas mediating memory; however, the role of this receptor on memory remains little explored. Objective: First, demonstrating the associative nature of Pavlovian/instrumental autoshaping (P/I-A) task, rats were exposed (three sessions) to CS-US (Pavlovian autoshaping), truly random control, free operant, and presentations of US or CS, and they were compared with rats trained-tested for one session to the P/I-A procedure. Also, effects of the 5-HT receptor agonist LP-211 administered intraperitoneally after training was determined on short- (1.5 h) and long-term memory 24 and 48 h) and on scopolamine-induced memory impairment and cAMP production. Methods: Autoshaping and its behavioral controls were studied. Other animals were subjected to an autoshaping training session and immediately afterwards were given (intraperitoneal) vehicle or LP-211 (0.1-10 mg/kg) and/or scopolamine (0.2 mg/kg) and tested for short-term memory (STM) and long-term memory (LTM); their brains were extracted for the cAMP ELISA immunoassay. Results: P/I-A group produced the higher %CR. LP-211 did not affect STM; nonetheless, at 0.5 and 1.0 mg/kg, it improved LTM. The 5-HT receptor antagonist SB-269970 (SB; 10.0 mg/kg) alone had no effect; nevertheless, the LP-211 (1.0 mg/kg) LTM facilitation was reversed by SB. The scopolamine (0.2 mg/kg) induced-decrement in CR was accompanied by significant increased cAMP production. The scopolamine-induced decrement in CR and increments in cAMP were significantly attenuated by LP-211. Conclusions: Autoshaping is a reliable associative learning task whose consolidation is facilitated by the 5-HT receptor agonist LP-211. [ABSTRACT FROM AUTHOR]

Although post-traumatic stress disorder (PTSD) and addiction are very different disorders, both are characterized by hyperreactivity to trauma- or drug-related cues, respectively. We investigated whether an appetitive conditioning task, Pavlovian conditioned approach, which predicts vulnerability to reinstatement of cocaine-seeking, also predicts fear incubation, which may be a marker for vulnerability to PTSD. We classified rats based on whether they learned to approach and interact with a food predictive cue (sign-trackers), or, whether upon cue presentation they went to the location of impending food delivery (goal-trackers). Rats were then exposed to extensive Pavlovian tone-shock pairings, which causes the fear response to increase or “incubate” over time. We found that the fear incubation effect was only present in sign-trackers. The behavior of goal-trackers was more consistent with a normal fear response–it was most robust immediately after training and decayed slowly over time. Sign-trackers also had lower levels of brain-derived neurotrophic factor (BDNF) protein in the prefrontal cortex than goal-trackers. These results indicate that, while many factors likely contribute to the disproportionate co-occurrence of PTSD and substance abuse, one such factor may be a core psychological trait that biases some individuals to attribute excessive motivational significance to predictive cues, regardless of the emotional valence of those cues. High levels of BDNF in the prefrontal cortex may be protective against developing excessive emotional and motivational responses to salient cues. [ABSTRACT FROM AUTHOR]

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist ofNMDA glutamate receptors and a7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an auto shaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence. [ABSTRACT FROM AUTHOR]

A cue associated with a rewarding event can trigger behavior towards the cue itself due to the cue acquiring incentive value through its pairing with the rewarding outcome ( i.e. , sign-tracking). For example, rats will approach, press, and attempt to “consume” a retractable lever conditioned stimulus (CS) that signals delivery of a food unconditioned stimulus (US). Attending to food-predictive CSs is important when seeking out food, and it is just as important to be able to modify one's behavior when the relationships between CSs and USs are changed. Using a discriminative autoshaping procedure with lever CSs, the present study investigated the effects of orbitofrontal cortex (OFC) lesions on sign-tracking and reversal learning. Insertion of one lever was followed by sucrose delivery upon retraction, and insertion of another lever was followed by nothing. After the acquisition phase, the contingencies between the levers and outcomes were reversed. Bilateral OFC lesions had no effect on the acquisition of sign-tracking. However, OFC-lesioned rats showed substantial deficits in acquiring sign-tracking compared to sham-lesioned rats once the stimulus-outcome contingencies were reversed. Over the course of reversal learning, OFC-lesioned rats were able to reach comparable levels of sign-tracking as sham-lesioned rats. These findings suggest that OFC is not necessary for the ability of a CS to acquire incentive value and provide more evidence that OFC is critical for modifying behavior appropriately following a change in stimulus-outcome contingencies. [ABSTRACT FROM AUTHOR]

Four pigeons and eight chickens received autoshaping training where a keylight (conditioned stimulus) signaled response-independent deliveries of water (unconditioned stimulus). Pigeons drink while keeping their beaks submerged in water and moving their beaks to create suction ("mumbling"), whereas chickens drink by trapping a small amount of water in their mouths and then lifting their heads so the water trickles down. This experiment tested whether these and other species-specific differences in drinking and related behaviors of pigeons and chickens would be reflected in the form of conditioned (autoshaped) responding. Touchscreens and videotapes were used for data recording. Results showed that chickens moved their heads more than pigeons when drinking (unconditioned response). The birds also differed in conditioned responding in the presence of the keylight: Pigeons produced more keyswitch closures and mumbled at the keylight more than chickens whereas chickens scratched more than pigeons. In conclusion, with this unique comparative method that employed identical contingencies and comparable deprivation levels, species-specific differences in unconditioned responses and, more importantly, differences in their corresponding conditioned responses were observed. [ABSTRACT FROM AUTHOR]

The author discusses the effectiveness of using 5-hydroxytrptamine (HT)7 receptor stimulation in treating amnesia and memory dysfunction. Topics include the stimulation of 5-HT7 receptor using the selective serotonin reuptake inhibitor, the significant effect of receptor in short-term memory and error reduction, and the cyclic adenylic acid (cAMP).