Emotional Feelings and Drug Addictions

1. Emotional Feelings and Drug Addictions Jaak Panksepp & Jeff Burgdorf J.P. Scott Center for Neuroscience, Mind and Behavior Department of Psychology Bowling Green State University & Falk Center for Molecular Therapeutics, Northwestern University

2. Mental Processes & Addictions Psychology has become the impoverished step-child in the neuroscience crusade to understand addictions. Because we have neglected the Neuroscience of Affective Feelings

3. Amphetamine induced euphoria • A PET study with the DA receptor antagonist raclopride • DA binding in the accumbens was associated with drug induced euphoria. Drevets WC et al. (2001) Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria. Biological Psychiatry, 49, 81-96.

4. Intranasal Methylphenidate administration Drug vs. $ Choice Arousal Drug Liking Stoops, Glaser & Rush (2003). Drug and Alcohol Dependence, 71: 179-186.

5. From: Volkow, Fowler & Wang (2002)

6. "We might well ask would drug addiction exist if drugs did not change our internal feelings?" Panksepp, J (2002) Foreword "The Evolutionary Neuroethology of Paul MacLean" (G.A Gory & R. Gardner, eds), Praeger, London. (p. xx)

7. "We might well ask would drug addiction exist if drugs did not change our internal feelings?" Panksepp, J (2002) Foreword "The Evolutionary Neuroethology of Paul MacLean" (G.A Gory & R. Gardner, eds), Praeger, London. (p. xx) "Clearly the answer is NO -- and not only for members of our own species."

8. Some Obvious Theses Concerning Brain, Mind & Emotions • The fundamental emotional/affective systems of the mind reflect various evolutionarily adaptive functions of the brain. • In our modern search to understand the nature of the mind, we neuroscientists often choose to forget that a key function of the brain is to generate psychological processes that regulate behavior. • Thinking, perceiving, feeling, and behaving (and getting addicted) are not just properties of brain molecules. To understand how brains generate addictions we do need psychological perspectives.

9. To understand drug addiction we must understand the nature of affective processes.

10. To understand drug addiction we must understand the nature of affective processes. Affective states of the nervous system are emergent evolutionary properties of complex neural dynamics that need to be properly conceptualized and linked to the concrete (and multi-dimensional) brain processes from which they emerge.

11. What is the Nature of Affect?(A Rough Taxonomy) 1) Pleasures & Pains of Sensation (Consummatory Rewards, Drives, Punishments) 2) Emotional/Affective Arousals (Causal Core--Instinctual Brain Action Systems) 3) Post Arousal Relief/Satisfaction/Distress (Homeostatic Moods)

12. Oxford University Press, 1998

13. Perhaps the only comprehensive survey of how affective processes emerge from neural activities Oxford University Press, 1998

14. Conjecture If Human “pipe dreams” (or subjective reality) were not more enticing than external reality –there would be no addictions. Addictions do not exist without changes inaffective feelings (various experiences of goodness and badness)

15. Panksepp & Bishop (1981). Brain Res Bull, 7, 405-410. Mu Opioids Endorphins (Long-term ++) Delta Opioids Enkephalins (Short-term +) Kappa Opioids Dynorphins (Aversive)

16. Lets Start With Banana Addiction

17. Lets Start With Banana Addiction Brain Opioids and the Pleasure of Sensation

18. But Pleasure is a Fuzzy Concept There are many different kinds of Pleasure For instance, pleasures of companionship

19. Lets Consider Social Addiction

20. Attachment / Social Bonding Chemistries Intersubjectivity Opioids (1970s) Oxytocin (1990s) Prolactin (soon)

21. Attachment / Social Bonding Chemistries Social bonding may be an addictive process Opioids (1970s) Oxytocin (1990s) Prolactin (soon)

22. Brain Opioids and the Pleasure of Social Feelings

23. CONTACT COMFORT Brain Opioid Receptors blocked by naloxone

25. Panksepp, et al. (1978). Biol. Psychiatry,9, 213-220.

26. Panksepp, J. (2003). Science, Oct 10th.

27. Implications: One reason people get addicted to opiates is because they experience a level of “social pain” (isolation-distress)which makes opiates especially attractive because they provide comfort. Addiction is not just a matter of “pleasure” and distress alleviation It is also a matter of Desire

28. Desire/Seeking System

29. SEEKING System Jim Olds Reward, Pleasure, Reinforcement System

30. History of the Theories of Brain-Stimulation “REWARD” Reward, Reinforcement & Pleasure (Olds, et al. 1954-Present) Dual Process Hypothesis: Drive and Reward (Deutsch, 1963). Ethological: Approach & Avoidance (Glickman & Schiff, 1967) Unified Incentive Hypothesis (Trowill, Panksepp & Gandelman , 1969) Full Plasticity of the Underlying Substrates (Valenstein et al., 1970) Learning BRAIN Dopamine Systems characterized Unified Hedonia/Pleasure Concept (Wise, 1982—RIP 1993) Wanting/Liking Concept (Robinson & Berridge, 1993-present) Foraging/Expectancy/SEEKING Concept (Panksepp, 1971-present) STATE views Information-Processing views:1990 – Present,Reward Prediction Error (Schultz); Associative processes in addiction (Everitt & Robbins) etc, etc, etc. Consensus: Mesolimbic/Mesocortical Dopamine Pathways are involved in appetitive motivation rather than consummatory reward

31. The Dopamine part of it Anatomy of the Desire/SEEKING System

32. Appetitive and Consummatory Behavior after DA blockade in the Nuc. Accumbens Wanting-SEEKINGLiking cis-flupentixol Ikemoto, S. & Panksepp, J. 1996 Behav. Neurosci.,110, 331-345.

33. 10-7 10-6 10-5 Data according to Knutson et al. (2001) Human brain Anticipating monetary reward

34. Use-Dependent Plasticity Sensitization of the SEEKING System

35. I want it. . .

36. I want it. . . And I want it NOW!

37. Amphetamine Sensitization 200 100 180 80 160 60 140 40 120 20 100 80 0 60 -20 40 -40 20 Food Seeking 0 Amphetamine CPP 2x Sal 2x Am5.0 100 80 60 40 20 0 -20 (Nocjar & Panksepp 2002) -40 Sexual Pursuit

38. ADHD, Childhood Impulsivity & PLAY “ADHD” Kids are a bit short in the Frontal Lobes (5%).

39. Panksepp, et al. (2002) Consciousness & Emotion, 3: 7-19.

40. Sensitization VEHICLE METHYLPHENIDATE Panksepp, et al. (2002) Consciousness & Emotion, 3: 7-19.

41. How Do You Measure Positive Feelings in Animals?

42. Measurement of positive emotion • Humans • Subjective self report • Facial & vocal displays (i.e. Duchenne smile) • Approach behavior • Other Animals • Emotional Actions • Facial & vocal displays • Approach behavior ty.cooldog.com/images/SixMonth/ SittingUp5.jpg Gallery .c onsumerreview.com/ pcphoto/480/56687.jpg

43. Play as an index of joy in rats • All mammals tested engage in vigorous play behavior during adolescence. • Rats find rough-and- tumble (RAT) play to be highly rewarding. • We monitor RAT play primarily by counting dorsal contacts and pinning behaviors. Dorsal contact www.epub.org.br/cm/n13/mente/ laughter/rat17.jpg exn.ca/news/Images/ 19980505-ratpin.jpg

44. Ultrasonic Calls: an overview Knutson, Burgdorf & Panksepp (2002). Psychological Bulletin, 128: 961-977.

45. 50-kHz calls:a rat model of positive emotions? Animal Laughter? • 50-kHz chirps are elicited by a wide variety of rewards.

46. 50-kHz calls:a rat model of positive emotions? • Panksepp & Burgdorf (2003). “Laughing rats” and the evolutionary antecedents of human joy, Physiology & Behavior, 79: 533-547. • Aversive stimuli suppress 50-kHz chirps Animal Laughter?

47. Ultrasonic Calls:Affective self-report Pleasureable Drugs Positive Affect Sounds Aversive Drugs Negative Affect Sounds

48. Drug reward and aversion 50 kHz Appetitive Chirps 22 kHz Aversive Squeals Burgdorf, J. et al. (2001) Psychopharmacology, 155, 35-42.

49. Anticipation of reward From: Burgdorf, Knutson & Panksepp (2000)

50. Dopamine helps trigger 50-kHz Calls From: Burgdorf, Knutson, Ikemoto & Panksepp (2001)