Negative Reinforcement

Whereas positive reinforcement occurs when presentation of a drug increases the probability of a response to obtain the drug, negative reinforcement occurs with alleviation of an existing aversive state or alleviation of a drug-generated aversive state (e.g., withdrawal).

Negative reinforcement models (17, 18) centre on the concept of allostasis (19) in which, during the addiction cycle, from initial use to compulsive abuse, multiple neurotransmitter and hormonal systems are recruited to maintain normal reward function but “at a price”.  Reward function becomes the function of both dopaminergic and stress mechanisms (although other neurotransmitters are implicated).

In the addiction cycle, dopamine and stress chemicals begin to act as “opponent processes” with the acute effects of initial drug intake followed by the recruitment of “opposing systems” such as activation of brain stress systems like corticotropin-releasing factor (CRF) and norepinephrine (NE) in order to oppose (in terms of homeostasis) the initial hedonic effects of a drug by a slowly developing counteracting process that becomes larger over time (20).

Through increased drug use, there is an eventual hypofunctioning of neurotransmitter systems involved in positive reinforcement, in dopamine pathways, demonstrated by decreases in D2 receptor expression and decreases in dopamine release and a recruitment of systems involved in negative emotional states that provide the motivation for negative reinforcement – e.g. increased CRF.

These “allostatic-like” changes create negative affective states which get larger with repeated drug use, representing a true “sensitization”, addictive behaviours driven by negative reinforcement, i.e. to alleviate this negative affect (NA).

This is the theoretical rationale of one prominent negative reinforcement model, the Hedonic Homeostatic Dysregulation (HD) Model, mainly associated with Koob and le Moal (18), which posits that the addiction cycle consists of three phases: 1) preoccupation-anticipation; 2) binge-intoxication; and 3) withdrawal-NA.

Addiction progresses from seeking positive reinforcement in phase 1, to a desire to  alleviate NA creating an enhanced sensitivity to conditioned cues in phase 2, in which  dopamine contributes to neuroplastic changes associated with conditioned responses to “cues” and plastic changes in stress systems involved in the enhanced sensitivity to NA. Stress appears to enhance the effect of brain circuits involved in reward processing and in attentional and mnemonic bias for drug use reminders (21).

The compulsive craving-based phase 3 has characteristics of a compulsive disorder (22) and recruits the cortico-striatal-thalamic loop (C-L-S), as with OCD, with compulsion defined as repetitive behaviours to prevent or reduce anxiety or distress, not to provide pleasure or gratification (23).

As with Everrit and Robbins, drug addiction represents a gradual change in associative structures to more automatic or habitual, with engagement of dorsal striatal (DS) mechanisms.

Evidence for this model comes from imaging studies of addicted individuals during withdrawal or protracted abstinence, which show decreases in D2 receptor density (24) and increases in CRF and glucocorticoids (GCs) (21).

References

17. Koob, GF, LeMoal M (2001): Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24: 97–129.
18. Koob GF, Le Moal M (1997): Drug abuse: hedonic homeostatic dysregulation. Science 278:52–58.
19. McEwen BS (1998): Stress, adaptation, and disease: Allostasis and allostatic load. Annals of the New York Academy of Sciences 840 (1): 33-44.
20. Solomon RL, Corbit, JD (1974). An opponent-process theory of motivation: 1. Temporal dynamics of affect. Psychol Rev 81: 119–145.
21. Duncan E Boshoven W, Harenski K, Fiallos A, Tracy H, Jovanovic T, et al  (2007): An fMRI study of the interaction of stress and cocaine cues on cocaine craving in cocaine-dependent men. The American Journal on Addictions 16: 174–182.
22. Koob GF, Volkow N D (2010): Neurocircuitry of addiction. Neuropsychopharmacology 35(1): 217-238.
23. American Psychiatric Association (2000): Diagnostic and Statistical Manual of Mental Disorders 4^th ed. Washington, DC: Author.
24. 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.