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| The Role of Conditioned Reinforcement in Learning and Memory Processes: Implications for Drug Addiction |
| Saturday, May 23, 2015 |
| 2:00 PM–3:50 PM |
| 008A (CC) |
| Area: BPH/EAB; Domain: Basic Research |
| Chair: Jennifer Laude (University of Kentucky) |
| Discussant: Federico Sanabria (Arizona State University) |
| Abstract: Theoretical models of drug addiction assert that drug cues come to be associated with drug-taking and the rewarding effects of the drug. These cues are said to have acquired conditioned reinforcing properties, much like the drug itself, and increase approach to the associated drug. It is known that individuals who attribute heightened degrees of conditioned reinforcement to drug stimuli are more vulnerable to drug abuse-related behavior in that said cues can precipitate or prolong use once an episode has begun. However, the exact mechanisms underlying the operation of conditioned reinforcers and their translation to drug abuse are not well understood. To this point, translational research on how conditioned reinforcement contributes to abuse through learning and memory mechanisms will be discussed from both pre-clinical and clinical perspectives. Collectively, the data presented demonstrate: 1) the utility of a new-response acquisition for studying drug-conditioned reinforcement, 2) substance abuse vulnerability may be related to propensities to learn stimulus-reinforcer relationships during drug-taking which accrue value and persist despite negative consequences, 3) drugs may potentiate the conditioned reinforcement of stimuli associated with their acquisition and use and 4) potential processes by which drug memories and responses are acquired/conditioned that can influence drug-taking. |
| Keyword(s): conditioned reinforcement, drug-seeking/taking, learning/memory mechanisms, translational research |
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| Using New-Response Acquisition to Study Opioid-Conditioned Reinforcement in the Rat |
| JEREMIAH W. BERTZ (University of Michigan), James H. Woods (University of Michigan) |
| Abstract: The conditioned reinforcing effects of opioid-associated stimuli may significantly exacerbate opioid abuse behaviors. However, the determinants of performance with opioid-conditioned reinforcement have not been well characterized. The present experiments used new-response acquisition to test stringently for the conditioned reinforcing effects of a stimulus paired with the opioid agonist, remifentanil. First, in Pavlovian conditioning (PAV) sessions, rats received response-independent IV injections of remifentanil and presentations of a light–noise stimulus. Injections and stimuli either always co-occurred (“paired PAV”) or occurred independently of each other (“random PAV”). Next, in instrumental acquisition (ACQ) sessions, all animas were given access to two novel nose-poke manipulanda. Active nose-poke responses produced the stimulus alone, whereas inactive nose-poke responses had no scheduled consequences. Using these procedures, we have shown that the stimulus acts as a conditioned reinforcer: animals acquire nose-poke responding (i.e., active > inactive) after paired PAV, but not after random PAV. We have, furthermore, shown that responding with opioid-conditioned reinforcement is sensitive to several environmental and pharmacological/neurobiological factors: remifentanil dose and number of injections during PAV, reinforcement schedule during ACQ, animals’ sex, and dopamine D2 receptor activation. These experiments demonstrate the usefulness of new-response acquisition for studying drug-conditioned reinforcement. Financial support: NIDA T32DA07268, R01DA024897, R01DA032943 |
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| The Relative Role of Stimulus-Reinforcer vs. Response-Reinforcer Relationships in Sign-tracking, goal-tracking, and Subsequent Conditioned Reinforcement within Pavlovian Conditioned Approach |
| JOSHUA BECKMANN (University of Kentucky), Jonathan Chow (University of Kentucky) |
| Abstract: Individuals that have a propensity to sign-track, instead of goal-track, to an appetitive Pavlovian conditioned stimulus are also more vulnerable to drug abuse-related behavior; however, the behavioral mechanisms that mediate these response types remain largely unknown. Here, we used different conditioned stimuli to specifically elicit sign- and goal-tracking responses within individual rats using a Pavlovian conditioned approach task. We then determined the relative efficacy of a stimulus associated with sign-tracking vs. goal-tracking to function as conditioned reinforcers. The stimulus associated with sign-tracking served as a more robust conditioned reinforcer, was exclusively chosen over a stimulus associated with goal-tracking (when both stimuli were equally predictive of the same reinforcer), and choices for the stimulus associated with sign-tracking were discounted hyperbolically as a function of increases in the odds against reinforcement. Furthermore, subsequent testing under omission and extinction contingencies indicated that sign-tracking was governed by a stimulus-reinforcer relationship, while goal-tracking was mediated by a response-reinforcer relationship. Collectively, these data suggest that individual differences in substance abuse vulnerability may be related to the relative propensity to learn stimulus-reinforcer vs. response-reinforcer relationships during drug-taking behavior, where stimulus-drug relationships accrue greater value and are more persistent in the face of negative consequences. |
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| Acute Effects of Alcohol on Encoding and Consolidation of Memory for Alcohol-Related Stimuli |
| JESSICA WEAFER (University of Chicago), David Gallo (University of Chicago), Harriet de Wit (University of Chicago) |
| Abstract: Addiction is characterized by powerful drug-related memories that exert a substantial and maladaptive influence over behavior. The idea is that drugs act directly on the motivational memory systems that enable organisms to learn about stimuli predicting outcomes important for survival. Thus, drugs may potentiate the conditioned reinforcement of stimuli associated with their acquisition and use. The current study examined the effects of alcohol (0.8 g/kg) on memory for alcohol-related and neutral beverage stimuli when administered either prior to stimulus viewing (Encoding group; n=20) or immediately following stimulus viewing (Consolidation group; n=20). A third group received placebo both prior to and following stimulus viewing (Control group; n=19). Exactly 48 hours after viewing the stimuli participants attended a retrieval session during which they performed a surprise cued recollection and recognition test of the stimuli in a drug-free state. Alcohol impaired cued recollection in the Encoding group for neutral but not alcohol-related images. By contrast, alcohol enhanced recognition memory in the Consolidation group for alcohol-related but not neutral beverage stimuli. These findings have potentially important implications for understanding associations between the conditioned reinforcing properties of alcohol-related stimuli and alcohol effects on memory. |
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| Alcohol-Conditioned Contexts Alter Cognitive Function, Alcohol Subjective Experiences, and Increase Alcohol Drinking. |
| EMMA CHILDS (University of Chicago), Harriet de Wit (University of Chicago) |
| Abstract: Powerful memories formed between drug effects and the cues surrounding drug experiences are a major barrier to the successful treatment of addiction and can cause relapse even after long periods. However, treatment approaches that target drug cue-elicited craving are not overly successful, perhaps because cravings are not common to all addictions or relapse episodes. Thus, there is a need to better understand the processes by which drug memories are acquired, the range of responses, other than craving, that are conditioned, and the ways in which they influence drug-taking. Recently, we have developed a new laboratory model to establish conditioned associations between drugs and contexts in human volunteers. In this study, we show that healthy moderate drinkers come to exhibit a place preference for a context paired with alcohol administration. In comparison to the no alcohol-paired context, subjects exhibited poorer working memory performance yet faster reaction times in the alcohol-paired context. Subjects also reported less negative subjective responses to alcohol and chose to consume significantly more alcohol drinks in the alcohol-paired context. The implications of these findings include that approaches to enhance cognitive resources and improve executive functioning in the conditioned environment may help drinkers to control their alcohol use. |
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