(a) The return of impulsive behaviour in highly impulsive rats following withdrawal and abstinence from cocaine self-administration. The data shown are premature responses in a 5-CSRTT. (i) Highly impulsive rats respond prematurely before any cocaine experience and (ii) their impulsivity is reduced following sessions of cocaine self-administration; (iii) but premature responding returns to pre-cocaine levels following an extended period of withdrawal (J. W. Dalley 2007, unpublished observations). Filled circles, high; open circles, low. (b) Impulsive rats show an increased propensity to relapse after abstinence. (i) Impulsive and non-impulsive rats were trained to seek and take cocaine under a chained schedule. (ii) Subsequently, 50% of the seeking responses were followed unpredictably by punishment and 50% by access to the taking lever; this results in the suppression of drug seeking. (iii) Following a further preiod of abstinence, when no cocaine was available rats were returned to the self-admininistration setting in which seeking responses resulted in the presentation of a cocaine-associated conditioned reinforcer, but no drug. (iv) Impulsive rats showed much higher numbers of seeking responses than low impulsive rats and hence showed a greater propensity to ‘relapse’. Filled circles, high; open circles, low.

Within striatum serial processing underlies the establishment of cocaine-seeking habits. (a) Schematic of the intrastriatal dopamine-dependent spiralling circuitry functionally connecting the ventral with the dorsal striatum in the rat (modified from Belin & Everitt 2008). The spiralling loop organization is depicted as the alternation of pink and black arrows from the ventral to the more dorsal parts of the circuit, i.e. from the AcbS (yellow) to the AcbC (light blue) via the ventral tegmental area (pink) and from the AcbC, via the substantia nigra to the dorsal striatum (dark blue). (b) Cocaine seeking is dose dependently impaired by bilateral infusions of the DA receptor antagonist α-flupenthixol (depicted as green dots) into the DL striatum. α-Flupenthixol infusions into the DL striatum dose dependently decreased responding on the active lever under a second-order schedule of cocaine reinforcement, but had no effect on responding on the inactive lever (Belin & Everitt 2008). (c) Disconnecting the AcbC from the dopaminergic innervation of the dorsal striatum impairs habitual cocaine seeking. In unilateral AcbC-lesioned rats, the AcbC relay of the loop is lost on the one side of the brain. However, on the non-lesioned side, the spiralling circuitry is intact and functional. When α-flupenthixol (green dots) is infused in the DL striatum contralateral to the lesion it blocks the DAergic innervation from the midbrain, impairing the output structure of the spiralling circuitry on the non-lesioned side of the brain. Therefore, this asymmetric manipulation disconnects the core of the nucleus accumbens from the DL striatum bilaterally and greatly diminishes cocaine seeking (figure adapted with permission from Belin & Everitt (2008)).