A Critique of the Dopamine Model



Theoretical challenges to positive reinforcement models:-


  1. Lack of evidence for increased brain levels of dopamine in the addiction cycle – the increase in dopamine receptors, that the IS model proposes, is not demonstrated in human studies which demonstrate down-regulation of the mesolimbic dopaminergic system in alcohol, cocaine and methamphetamine- dependent persons (24), implying a hypo-dopaminergic rather than a hyper-dopaminergic state.
  2. Substance-related cues elicit a combination of both reward “appetitive” as well as a stress-based “aversive” response – stress, as well as dopaminergic systems, must be implicated in response to cues. Both cue- and stress-induced craving appear to cause anxiety and negative emotion, respectively, indicating a persistence of distress in the context of exposure to these triggers (34). This emotional response supports the notion of a stress-like challenge state of wanting, which motivates addicted individuals towards regaining a transient homeostasis as mentioned in the HD model (17).
  3. Dopamine deficit is unlikely to be the only component in incentive salience – lack of support for increased levels of dopamine in addicted individuals suggests that the hypersensitivity to substance-related cues cannot solely be accounted for by dopaminergic mechanisms. Berridge and Robinson (26) have provided insight into this seeming paradox by distinguishing between baseline versus cue-related changes in dopamine levels, suggesting that substance-induced dopamine release in the brain is decreased in individuals with a long history of substance abuse but that a marked increase in DA levels occurs when these individuals are presented with substance-associated stimuli. Elaborating on these findings, we hypothesize that the hypo-dopaminergic baseline may be the consequence of the effects of chronic stress but that upon encountering a substance-related cue, the individual may experience stress-augmented dopaminergic activity, as part of processes aimed at return to a new hedonic setpoint (17).
  4. IS, as measured by cue reactivity, may not be a major predictor of relapse – there is evidence that stress and NA predict relapse more reliably than external cues (28, 29). By focussing on purely dopaminergic-based/pathological wanting as the main factor in prompting relapse, IS theory neglects evidence that challenges the main theoretical assertion of the positive reinforcement models by failing to explain why stress (e.g. interpersonal relationships) is a major determinant in relapse.
  5. Substance-related cues are more potent predictors of relapse when combined with NA –

Koob and le Moal have suggested the predictive power of substance-related cues is greatly increased in the context of stress. Such interactions have been observed in animal studies across a variety of substances (i.e., alcohol, cocaine, heroin) and types of stressors (i.e., pharmacologic, footshock) (30, 31) and indicate that stress can enhance the reinforcing impact of cue-associated stimuli (17).

  1. Craving or pathological wanting is generally measured in terms of physiological stress response, so unlikely to be purely mediated through dopaminergic processes – one of the experimental methodologies developed from the IS paradigm, cue reactivity, is partly measured by stress responses, for example, galvanic skin conductance or cortisol levels, thus implicating stress in the craving state (32). Further evidence against a predominant focus on dopamine comes from the finding that craving can also be triggered by stress (34).
  2. The IS model does not account for all the brain regions that are reported to be activated during craving – the original IS model appears to implicate the VS in wanting. However, there is evidence of involvement of a much more extended “reward” network, including the BLA, hippocampus and PFC and DS (14). There is little consideration of the role of the DS in the habit-like compulsive seeking/using of substances although studies show dopaminergic and stress mechanisms are implicated in prompting of DS-based substance-related compulsive behaviour (35) and in line with addiction severity.
  3. No role elucidated for negative reinforcement in the “must do” compulsive behaviour in addiction – stress mechanisms are implicated in prompting of substance-related compulsive behaviour (35) via activation of the DS.





  1. Franken IH (2003): Drug craving and addiction: integrating psychological and neuropsychopharmacological approaches. Progress in Neuro-Psychopharmacology and Biological Psychiatry  27(4):  563-579.
  1. Koob, GF, LeMoal M (2001): Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24: 97–129.
  1.  Volkow N D, Fowler J S, Wang G J (2002): Role of dopamine in drug reinforcement and addiction in humans: results from imaging studies. Behavioural Pharmacology 13(5-6): 355-366.      26. Robinson TE, Berridge KC (2008). The incentive sensitization theory of addiction: some current issues. Philosophical Transactions of the Royal Society B: Biological Sciences, 363(1507): 3137-3146
  1. Nordfjærn, T (2011): Relapse patterns among patients with substance use disorders. Journal of Substance Use 16(4): 313-329. 29. Cooney NL, Litt MD, Morse PA, Bauer LO, Gaupp L (1997): Alcohol cue reactivity, negative mood reactivity, and relapse in treated alcoholic men. Journal of Abnormal Psychology 106: 243-250.
  1. Banna KM, Back SE, Do P, See RE (2010): Yohimbine stress potentiates conditioned cue-induced reinstatement of heroin-seeking in rats. Behavioural Brain Research, 208(1): 144-148.
  1. Liu X, Weiss F (2002): Additive effect of stress and drug cues on reinstatement of ethanol seeking: exacerbation by history of dependence and role of concurrent activation of corticotropin-releasing factor and opioid mechanisms. The Journal of Neuroscience, 22 (18): 7856-7861.
  2. Sinha R, Catapano D, O’Malley S (1999): Stress-induced craving and stress response in cocaine dependent individuals. Psychopharmacology 142(4): 343-351.
  3. Garland EL, Gaylord S A, Boettiger C A, Howard MO (2010): Mindfulness training modifies cognitive, affective, and physiological mechanisms implicated in alcohol dependence: Results of a randomized controlled pilot trial. Journal of Psychoactive Drugs 42(2): 177-192.
  4. Fox HC, Bergquist KL, Hong KI,  Sinha R (2007): Stress‐Induced and Alcohol Cue‐Induced Craving in Recently Abstinent Alcohol‐Dependent Individuals. Alcoholism: Clinical and Experimental Research 31(3): 395-403.
  5. Schwabe L, Dickinson A, Wolf OT (2011): Stress, habits, and drug addiction: a psychoneuroendocrinological perspective.Experimental and Clinical Psychopharmacology 19 (1): 53.






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