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A dual role for nicotine in reinforcement: the interaction between nicotine and non-drug cues (What can a lab rat tell

Will press for nicotine. A dual role for nicotine in reinforcement: the interaction between nicotine and non-drug cues (What can a lab rat tell us about why people smoke?). Nadia Chaudhri C enter for N euroscience U niversity of P ittsburgh. “nicotine is the drug in tobacco

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A dual role for nicotine in reinforcement: the interaction between nicotine and non-drug cues (What can a lab rat tell

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  1. Will press for nicotine A dual role for nicotine in reinforcement: the interaction between nicotine and non-drug cues (What can a lab rat tell us about why people smoke?) Nadia Chaudhri Center for Neuroscience University of Pittsburgh

  2. “nicotine is the drug in tobacco that causes addiction” Health Consequences of Smoking: Nicotine Addiction. A report by the Surgeon General, USDHHS, 1988 Why do people smoke?

  3. Nonpharmacological factors • Smoking cigarettes is more rewarding than isolated • nicotine delivery • De-nicotinized cigarettes reduce craving and withdrawal • Sensory stimuli, such as visual and olfactory cues • associated with smoke are reinforcing

  4. Nonpharmacological factors • Smoking cigarettes is more rewarding than isolated • nicotine delivery • De-nicotinized cigarettes reduce craving and withdrawal • Sensory stimuli, such as visual and olfactory cues • associated with smoke are reinforcing Do nonpharmacological stimuli impact nicotine self-administration in rats?

  5. Nonpharmacological stimuli DO impact nicotine reinforcement in rats Nicotine and nonpharmacological stimuli interact synergistically to result in high levels of operant behavior • Dual-reinforcing properties of nicotine: • Relatively weak, primary reinforcer • Enhance the reinforcing properties of behaviorally relevant, nonpharmacological environmental stimuli • Donny EC, Chaudhri N & Caggiula AR et al.(2003) Psychopharmacology

  6. Compound Visual Stimulus Infusion Signals Nic Delivery Cue Light (on) Nic + House Light (off) Nic - Fixed-ratio Reinforcement Schedule (60 min) FR 1 FR 2 FR 5 Progressive Ratio Reinforcement Schedule (4 hours) Responses : 3, 6, 10, 15, 20, 25, 32, 40 … Infusion # 1, 2, 3, 4, 5, 6, 7, 8 … Nicotine self-administration in rats • Male, Sprague Dawley rats • Reversed light/dark cycle • 20 g food per day • Prior food training

  7. Contingent nicotine + VS Acquisition of NIC-SA with or without VS

  8. Contingent nicotine + VS Contingent Saline + no VS Contingent Saline + VS Acquisition of NIC-SA with or without VS

  9. Contingent nicotine + VS Contingent nicotine + no VS Contingent Saline + no VS Contingent Saline + VS Acquisition of NIC-SA with or without VS

  10. Contingent nicotine + VS Contingent nicotine + no VS Contingent Saline + VS Nicotine + VS - additive Acquisition of NIC-SA with or without VS

  11. Acquisition of NIC-SA without VS: dose-response

  12. Interim summary • Nicotine does function as a primary reinforcer, • although this effect is relatively weak in the • absence of a nonpharmacological stimulus • 2. Nicotine interacts synergistically with non-drug stimuli to promote stable, high levels of operant behavior • Like nicotine, the VS we use is also a weak • primary reinforcer

  13. Smoking paradox • How does such a powerfully addictive behavior, smoking, emerge from such a weak primary reinforcer, nicotine? • How can a weak primary reinforcer, nicotine, • synergize with environmental stimuli to produce high rates of self-administration in rats (and smoking in people)? Is nicotine functioning as more than just a primary reinforcer?

  14. Will press for NIC + VS NIC Will press For VS Impact of contingency on reinforced behavior

  15. Impact of noncontingent NIC on responding for the VS Donny EC, Chaudhri N & Caggiula AR et al.(2003) Psychopharmacology

  16. Impact of noncontingent NIC on responding for the VS Donny EC, Chaudhri N & Caggiula AR et al.(2003) Psychopharmacology

  17. Interim summary Nicotine, delivered noncontingently, elevated responding for a weakly reinforcing, nonpharmacological stimulus, suggesting that nicotine can enhance the reinforcing properties of: Rats: Environmental stimuli in self-administration experiments Humans: Sight, smell, taste of cigarette smoke and other stimuli in environment while smoking. • Is noncontingent nicotine as effective at enhancing the reinforcing value of the VS across a range of doses, and does it impact motivation to obtain the VS when assessed using a progressive ratio reinforcement schedule? 2) Does noncontingent nicotine enhance the salience of all nonpharmacological stimuli equally?

  18. Impact of noncontingent NIC : dose-response

  19. Impact of noncontingent NIC : dose-response

  20. Impact of noncontingent NIC : dose-response

  21. Impact of noncontingent NIC on a PR schedule

  22. Impact of noncontingent NIC on a PR schedule

  23. Does noncontingent nicotine enhance the salience of all nonpharmacological stimuli equally? Test-day Pavlovian conditioning Days 1-14; levers retracted Group 1 - PAIRED Sucrose (60) Stimulus (30) Paired Group 2 - UNPAIRED Sucrose (60) Stimulus (30) 30 min Unpaired Pavlovian-to-Instrumental Transfer (Test-day) Day 15; levers extended; no sucrose; 30-min from 1st press STIMULUS = 5 second tone onset and 5 second house light offset Self-administration sessions (FR and PR) PAIREDUNPAIRED Saline + CR Saline + CR Contingent NIC + CR Contingent NIC + CR Noncontingent NIC + CR Noncontingent NIC + CR

  24. Impact of noncontingent NIC on a differentially reinforcing, nonpharmacological stimulus

  25. Impact of noncontingent NIC on a differentially reinforcing, nonpharmacological stimulus Paired Stimulus

  26. Impact of noncontingent NIC on a differentially reinforcing, nonpharmacological stimulus Paired Stimulus

  27. Impact of noncontingent NIC on a differentially reinforcing, nonpharmacological stimulus Unpaired Stimulus

  28. Impact of noncontingent NIC on a differentially reinforcing, nonpharmacological stimulus Unpaired Stimulus

  29. Impact of noncontingent NIC on a differentially reinforcing, nonpharmacological stimulus

  30. Impact of noncontingent NIC on a differentially reinforcing, nonpharmacological stimulus Paired Stimulus

  31. Impact of noncontingent NIC on a differentially reinforcing, nonpharmacological stimulus Unpaired Stimulus

  32. Impact of noncontingent NIC on a differentially reinforcing, nonpharmacological stimulus Unpaired Stimulus

  33. Impact of noncontingent NIC on a differentially reinforcing, nonpharmacological stimulus

  34. Interim summary • The reinforcement-enhancing effects of nicotine are not specific to one type of nonpharmacological stimulus, the VS • The ability of nicotine to enhance the reinforcing properties of a nonpharmacological stimulus depends on the reinforcing value of that stimulus • 3. Like self-administered nicotine, response-independent nicotine delivery can increase motivation to obtain nonpharmacological stimuli, as tested with a progressive ratio schedule

  35. Why do people smoke? “People smoke to receive nicotine” Primary Reinforcer: Behaviors that lead to nicotine delivery are strengthened • “Nicotine makes people smoke” • Reinforcement-Enhancing: Nicotine can amplify or • enhance the motivational/reinforcing properties of • other stimuli by a mechanism that is not dependent • on a predictable temporal (contingent) association • with either the stimuli or the behavior

  36. Caggiula Lab Tony Caggiula Alan Sved Eric Donny Matt Palmatier Xiu Liu Sheri Booth Maysa Gharib Laure Craven Prema Chaudhary Donna Pacelli Caroline Bouris Shannon Allen Peter Olausson NIDAHHMI

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