Conditioned brain-stimulation reward attenuates the acoustic startle reflex in rats.

The acoustic startle reflex (ASR) in rats is attenuated by a light paired with food or, in humans, by "pleasant" pictures. Rats were trained to barpress for lateral hypothalamus (LH) stimulation. ASR amplitudes were then measured at 4 intensities, with or without a light. Control rats that did not receive brain-stimulation reward (BSR) showed initially lower ASR amplitudes than did rats exposed to BSR, but both groups responded similarly with or without light. Next, experimental rats were given BSR in the presence of light but not in its absence. After conditioning, ASR amplitudes were reduced, and ASR thresholds were raised by a mean of 2.6 dB in the light but remained at preconditioning levels without light. No such change was found for control rats or rats with placements outside the LH. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Music-induced context preference following cocaine conditioning in rats.

Traditional models of drug-seeking behavior have shown that exposure to associated environmental cues can trigger relapse. These learned associations take place during repeated drug administration, resulting in conditioned reinforcement. Although considerable investigation has occurred regarding simple conditioned stimuli, less is known about complex environmental cues, particularly those that may be salient in human addiction. Recent studies indicate that music can serve as a contextual conditioned stimulus in rats and influence drug-seeking behavior during abstinence. The purpose of the present study was to further assess the effectiveness of music as a conditioned stimulus in rats, to determine rats' preferences for two contrasting pieces of music, and to determine rats' preferences for music versus silence. To this end, we created an apparatus that gave instrumental control of musical choice (Miles Davis vs. Beethoven) to the rats themselves. After determining baseline musical preference, animals were conditioned with cocaine (10 mg/kg) to the music they initially preferred least, with alternating conditioning sessions pairing saline with the music preferred most. The animals were subsequently tested in a drug-free state to determine what effect this conditioning had on musical preference. The results indicate that music serves as an effective contextual conditioned stimulus, significantly increasing both musical preference and locomotor activity after repeated cocaine conditioning. Furthermore, we found that rats initially favor silence over music, but that this preference can be altered as a result of cocaine-paired conditioning. These findings demonstrate that, after repeated association with reward (cocaine), music can engender a conditioned context preference in rats; these findings are consistent with other evidence showing that musical contextual cues can reinstate drug-seeking behavior in rats. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Competition between the conditioned rewarding effects of cocaine and novelty.

Access to novelty might provide an alternative learning history that competes with conditioned drug reward. We tested this suggestion in rats using a place conditioning procedure with cocaine and novelty. In Experiment 1, rats were conditioned with cocaine to prefer one side of an apparatus. In a subsequent phase, cocaine exposure continued; however, on the unpaired side, separate group of rats had access to novel objects, cocaine injections, or saline with no objects. Pairings with novel objects or cocaine shifted a preference away from the cocaine-paired environment during drug-free and drug-challenge tests. Experiment 2 tested novelty's impact when cocaine exposure was discontinued. The identical procedures were used except drug exposure ceased on the cocaine-paired side during the second phase. Both groups expressed a preference for the cocaine compartment. This preference was maintained for rats that did not have novel objects; however, rats that experienced novelty spent similar amounts of time in both compartments during both tests. Overall, the conditioned rewarding effects of novelty competed with those of cocaine as evidenced by a change in choice behaviors motivated by drug reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditions Favoring Superconditioning of Irrelevant Conditioned Stimuli.

Three appetitive conditioning experiments with rats found partial learning of complex XA+ , XB+ , XAB- (+ stands for reinforced; - stands for unreinforced) negative patterning discriminations with intermixed A+ and B+ trials (Experiment 1). AB+ trials (Experiment 2), and A+ , B+ , and AB+ trials (Experiment 3). In all experiments, differential responding emerged more slowly during the learning of the negative patterning discriminations than during learning of the XA+ , XB+ , XC- control discriminations. Additionally, the negative patterning groups responded more to X than to a separately reinforced Y on unreinforced test trials: thus, X derived superexcitatory properties. This pattern was reversed in the control groups. Results are consistent with theories that allow for different activation patterns when elements are combined. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Competition between novelty and cocaine conditioned reward is sensitive to drug dose and retention interval.

The conditioned rewarding effects of novelty compete with those of cocaine for control over choice behavior using a place conditioning task. The purpose of the present study was to use multiple doses of cocaine to determine the extent of this competition and to determine whether novelty’s impact on cocaine reward was maintained over an abstinence period. In Experiment 1, rats were conditioned with cocaine (7.5, 20, or 30 mg/kg ip) to prefer one side of an unbiased place conditioning apparatus relative to the other. In a subsequent phase, all rats received alternating daily confinements to the previously cocaine paired and unpaired sides of the apparatus. During this phase, half the rats had access to a novel object on their initially unpaired side; the remaining rats did not receive objects. The ability of novelty to compete with cocaine in a drug free and cocaine challenge test was sensitive to cocaine dose. In Experiment 2, a place preference was established with 10 mg/kg cocaine and testing occurred after 1, 14, or 28 day retention intervals. Findings indicate that choice behaviors mediated by cocaine conditioning are reduced with the passing of time. Taken together, competition between cocaine and novelty conditioned rewards are sensitive to drug dose and retention interval. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Growth of brain stimulation reward as a function of duration and stimulation strength.

The strength of a train of rewarding brain stimulation required to support a criterion level of operant performance declines hyperbolically as the duration is increased. This finding has been attributed to a process of leaky integration. However, the rate at which integration approaches asymptote has been shown to depend on stimulation strength, a finding that differs from the behavior of a simple leaky integrator. The authors replicate both findings and show that they are both well described by a new model that incorporates a hyperbolic strength-duration function, a logistic function mapping stimulation frequency onto reward intensity, and another logistic function mapping reward intensity onto performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned Activity and Instrumental Reinforcement Following Long-Term Oral Consumption of Cocaine by Rats.

Food-reinforced conditioned activity and instrumental responding were measured in rats after 50 weeks of continuous access to a cocaine-saccharin solution in their home cages. The elevation of conditioned activity produced by acute access to the cocaine-saccharin solution in the home cage during testing was abolished by long-term preexposure to the cocaine solution, an effect that was reversed by systemic administration of cocaine immediately prior to testing. By contrast, chronic cocaine preexposure enhanced instrumental responding for both cocaine-sucrose and pure sucrose solutions. These results support the idea that long-term cocaine exposure enhances subsequent reinforcement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Odor of Taste Stimuli in Conditioned "Taste" Aversion Learning.

The present research addresses whether rats can express odor aversions to the odor of taste stimuli. In Experiment 1, saccharin or salt were either mixed in distilled water, so the rats could taste and smell them, or presented on disks attached to the tubes' metal spouts so the rats could only smell them. Aversions were established to taste stimuli under both conditions. The results of Experiment 2 indicate that conditioning was to the odor of the tastes when they were presented on disks in Experiment 1, hence both taste and odor aversions were established by means of "taste" stimuli. Taste aversion learning thus may more properly be termed flavor aversion learning, with flavor referring to both taste and odor components. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned Inhibition of Cocaine Seeking in Rats.

Despite its potential relevance to the treatment of drug abuse, conditioned inhibition of drug seeking has not been systematically investigated before. In this study, rats could self-administer cocaine by lever pressing whenever a click or tone was present. Responding was not reinforced when a light was present. The light was presented simultaneously with the click (i.e., in an excitatory context) in 1 group, but the light was always presented alone in another group. When it was later presented in compound with the tone, the light was a highly effective conditioned inhibitor, suppressing cocaine seeking by 92% in the former group and by 74% in the latter. These results suggest ways to improve cue-oriented behavioral treatments for drug abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential control over drug-seeking behavior by drug-associated conditioned reinforcers and discriminative stimuli predictive of drug availability.

Conditioned stimuli (CSs) can control behavior either by activating responses when presented noncontingently or through their ability to maintain responding when presented contingently, that is, as conditioned reinforcers. In the present study, the extent to which drug-seeking behavior could be subject to these different types of stimulus control was studied by presenting to rats CSs that were either paired with each drug infusion or presented as discriminative stimuli (DSs) signaling the availability of drug. It was found that stimuli paired with either cocaine or heroin infusions increased drug seeking when presented contingent on responding, but not when presented noncontingently. By contrast, DSs that signaled cocaine availability increased drug seeking when presented either noncontingently or contingently. These results suggest that drug-seeking behavior can be influenced differentially by CSs and that conditioned reinforcers are especially important for maintaining prolonged sequences of drug-seeking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of two positive reinforcing stimuli: Pups and cocaine throughout the postpartum period.

This set of experiments investigated the appetitive or motivational processes underlying the performance of maternal behavior. The place preference paradigm was adapted to simultaneously investigate the reinforcing properties of cocaine and pups for maternal, lactating dams. These modifications allowed the authors to assess which stimulus, either a 10 mg/kg sc injection of cocaine or 3 pups, had the strongest reinforcing value. At Postpartum Days 10 and 16, the dams preferred the cocaine cue-associated chamber, whereas the dams tested at Postpartum Day 8 preferred the pup cue-associated chamber. Overall, the data revealed an interaction between the postpartum period at testing and the exhibited preference for cocaine or pups. Further testing will investigate the neural circuitry underlying the appetitive processes of each stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reduction of cocaine seeking by a food-based inhibitor in rats.

Environmental stimuli can exert a powerful influence over drug seeking and taking. For example, previous experiments found that combining multiple drug-related stimuli tripled drug seeking and doubled drug intake (L. V. Panlilio, S. J. Weiss, & C. W. Schindler, 1996, 2000), whereas a signal for the absence of cocaine (i.e., a drug-related inhibitor) dramatically reduced cocaine seeking in rats by over 90% (D. N. Kearns, S. J. Weiss, C. W. Schindler, & L. V. Panlilio, 2005). In the present experiment, a signal for the absence of food created through the A+/AB- conditioned inhibition paradigm also suppressed responding for cocaine by approximately 90%. Symmetrically, a signal for the absence of cocaine (i.e., a cocaine-based inhibitor) suppressed food seeking to a similar degree. These findings, consistent with the appetitive-aversive interaction theory of motivation, suggest that using inhibitors based on nondrug appetitive reinforcers might be a practical method of reducing drug seeking in human drug abusers and should be seriously considered for clinical test and application. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of CRH and energy balance in the modulation of brain stimulation reward.

The rewarding effect produced by electrical stimulation of some lateral hypothalamic sites is modulated by chronic food restriction and weight loss. The sensitivity of the rewarding effect to restriction predicts the modulation of brain stimulation reward (BSR) by the adiposity hormone, leptin. The present study examined the effect of corticotropin-releasing hormone (CRH) on the rewarding effect of stimulating restriction-sensitive and restriction-insensitive sites. Chronic food restriction reduced frequency thresholds for BSR in half of the subjects but had no effect in the others. CRH increased thresholds only in subjects in which the rewarding effect was insensitive to restriction. In contrast, frequency thresholds remained stable in nearly all rats with restriction-sensitive stimulation sites. These findings provide further evidence that sensitivity to food restriction is an important factor in determining the influence of hormones and neuropeptides on brain reward circuitry. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amygdala Central Nucleus Function Is Necessary for Learning, but Not Expression, of Conditioned Auditory Orienting.

In Pavlovian appetitive conditioning, rats often acquire 2 classes of conditioned responses: those whose form is determined by the reinforcer, and those whose form is determined by characteristics of the conditioned stimulus (CS). Consistent with the results of previous lesion studies, reversible inactivation of amygdala central nucleus function during pairings of an auditory CS with food prevented the acquisition of conditioned orienting responses specific to auditory CSs, whereas food-related conditioned behaviors were acquired normally. Neither inactivation nor posttraining neurotoxic lesions of the central nucleus affected the expression of previously acquired conditioned orienting. Thus, although the central nucleus is critical to the acquisition of information required for conditioned orienting to auditory cues, it is not needed for maintaining this information for later use. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned reinstatement of drug-seeking behavior with a discrete compound stimulus classically conditioned with intravenous cocaine.

The present study investigated the ability of a light and tone (LT) compound stimulus paired with cocaine infusions to reinstate cocaine-seeking behavior. Rats were trained to self-administer cocaine in the presence or absence of the LT during daily 3-hr sessions (maintenance). During Maintenance Days 5 and 10, rats underwent classical conditioning, whereby passive cocaine infusions were paired with either short-delayed, random, or no presentations of an LT. After extinction sessions, rats underwent test sessions in which the LT was presented in a noncontingent or response-contingent manner to measure conditioned cocaine-seeking behavior. The results demonstrated that response-contingent LT presentations significantly increased cocaine-seeking behavior and that the LT trained in a classical conditioning format transferred to an operant secondary reinforcer. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of behaviors elicited by electrical brain stimulation in dorsal brain stem and hypothalamus of rats.

Investigated 4 brain-stimulation phenomena elicited from both dorsal brain stem and hypothalamic sites, using a total of 20 male albino Holtzman Sprague-Dawley rats. Results show that (a) intracranial self-stimulation rate-intensity functions for dorsal brain stem and hypothalamic sites yielded very high (over 1,000 responses/15 min) to moderate (201-500 responses/15 min) response rates; (b) dextroamphetamine produced higher response rates than either levoamphetamine or saline at both dorsal brain stem and hypothalamic sites, indicating that noradrenergic dorsal brain stem fibers (or cell bodies) support intracranial self-stimulation; (c) dorsal brain stem and hypothalamic self-stimulation sites reliably produced escape behavior; (d) simultaneous stimulation of dorsal brain stem and hypothalamic sites at subthreshold intensities interacted to produce suprathreshold response rates. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measuring threshold shifts for brain stimulation reward using the method of limits.

Thresholds determined from the frequency of pulses and the current for rewarding brain stimulation were obtained from rats with lateral hypothalamic electrodes. The threshold, defined as the frequency or current corresponding to one-half the maximum response rate, was interpolated from reward summation functions. Daily trials of both ascending and descending sequences of frequency and current yielded no significant difference between order of presentation. While there was more variability in the maximum response rates across the sessions, neither frequency- nor current-based threshold evaluations yielded significant rate effects. Findings suggest that the threshold procedure is generally not influenced by the sequence of delivery of stimulus values and, thus, may be regarded as a reliable measure of the reinforcing properties of brain-stimulation reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experience-dependent effects of cocaine self-administration/conditioning on prefrontal and accumbens dopamine responses.

Experiments were performed to examine the effects of cocaine self-administration and conditioning experience on operant behavior, locomotor activity, and nucleus accumbens (NAcc) and prefrontal cortex (PFC) dopamine (DA) responses. Sensory cues were paired with alternating cocaine and nonreinforcement during 12 (limited training) or 40 (long-term training) daily operant sessions. After limited training, NAcc DA responses to cocaine were significantly enhanced in the presence of cocaine-associated cues compared with nonreward cues and significantly depressed after cocaine-paired cues accompanied a nonreinforced lever response. PFC DA levels were generally nonresponsive to cues after the same training duration. However, after long-term training, cocaine-associated cues increased the magnitude of cocaine-stimulated PFC DA levels significantly over levels observed with nonreinforcement cues. Conversely, conditioned cues no longer influenced NAcc DA levels after long-term training. In addition, cocaine-stimulated locomotor activity was enhanced by cocaine-paired cues after long-term, but not after limited, training. Findings demonstrate that cue-induced cocaine expectation exerts a significant impact on dopaminergic and behavioral systems, progressing from mesolimbic to mesocortical regions and from latent to patent behaviors as cocaine and associative experiences escalate. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The state of the reward comparison hypothesis: Theoretical comment on Huang and Hsiao (2008).

Rats avoid intake of a gustatory cue following pairings with a drug of abuse, such as morphine or cocaine. Despite the well-established rewarding properties of these drugs, the reduction in intake of the taste cue has been interpreted as a conditioned taste aversion for decades. In 1997, I proposed the reward comparison hypothesis suggesting that rats avoided intake of the drug-associated taste cue because the value of the taste cue pales in comparison to the highly rewarding drug of abuse expected in the near future. In this issue of Behavioral Neuroscience, A. C. W. Huang and S. Hsiao (see record 2008-17011-002) challenge the reward comparison hypothesis by showing parallels between amphetamine and LiCl-induced suppression of CS intake. This commentary addresses the current state of the reward comparison hypothesis in the context of the experiments completed by Huang and Hsiao and their new task-dependent drug effects hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)