Dopamine transmission during habitual responding for natural reinforcement
12 / 2007 - unknown
Addiction is often described as the development of a drug-taking habit. When a habit forms, behavior becomes automatized, highly stimulus bound, insensitive to outcome devaluation, and stimulus-response (S-R) associations are prioritized over action-outcome associations that were learned during early instrumental conditioning. Indeed, this set of properties resembles some (but certainly not all) of the behavioral features observed during drug addiction. It would, therefore, be useful to compare compulsive drug use with habits at a level other than behavior. In the proposed studies we will examine neurochemical and electrophysiological correlates of habit formation. In the work funded by the US parent grant, we are studying subsecond dopamine release in animals self-administering cocaine to identify neurochemical changes during the switch from recreational to compulsive drug use. One of the brain regions of interest is the dorsolateral striatum since dopamine in this anatomical locus has been highly implicated in habit formation and maintenance. The proposed work by the US partner will compliment these studies by examining changes in subsecond dopamine release in this area during the development of a food-taking habit. This will identify whether the (dopaminergic) neurochemical signature of the switch from recreational to compulsive drug use resembles that of the formation of habitual responding for a natural reinforcer.The Dutch partner will extend the work by carrying out electrophysiological recordings of medium spiny neurons in the dorsolateral striatum during the same shift to habitual responding for natural reinforcement.Importantly, to characterize the contribution of dopamine in the neuronal mechanisms underlying the shift, the combidrive will be used. The combidrive comprises fourteen moveable tetrodes surrounding a central microdialysis probe uniquely designed for local drug delivery without hampering neurophysiological recording. In this way the contribution of various dopamine receptor actions on the neurophysiological hallmarks of habit formation will be examined.However, it has been suggested that to become addicted, the formation of a habit is necessary but not sufficient. Among several possible conditioning factors, increased impulsivity and/or risk-taking behaviour (detected during adolescence) has been shown to favour the development of addictive behaviour and is related to ineffective impulse control by prefrontal cortical circuits. Consequently, both partners will carry out the above-mentioned studies in rats that have previously been characterized for risk-taking behaviour, selecting risk-prone and risk-aversive subjects. This allows a search for these distinctive factors regarding the development of habit formation. Future studies will make analogous electrophysiological recordings with the combidrive during compulsive drug taking. Collectively this work will provide neurochemical and electrophysiological evidence for the role of dopamine in habit formation, and allow the direct comparison of habitual responding for a natural reinforcer with compulsive drug use.