Role of the orbitofrontal cortex and the dorsal striatum in incentive motivation for cocaine.

Drug addiction involves increased incentive motivation for drug. Intermittent access to cocaine (IntA; 5-6 minutes ON, 25-26 minutes OFF, for 5-6 hours/session) enhances motivation to take the drug. The orbitofrontal cortex (OFC) and the dorsal striatum (DS) are part of a corticolimbic circuit that encodes incentive value and regulates reward-directed behaviour. We predicted that inactivation of the OFC, DS or both suppresses incentive motivation for cocaine after IntA experience. Male Wistar rats had IntA to cocaine (0.25 mg/kg/infusion) for 10 sessions. The rats developed a 'loading' pattern of intake, taking most of their cocaine in the first minute of each drug-available period. They also developed psychomotor sensitization to self-administered cocaine. We then measured incentive motivation for cocaine using a progressive ratio schedule of reinforcement (PR). Before some PR sessions, rats received microinfusions of a baclofen/muscimol cocktail (0.3 and 0.03 nmol/hemisphere, respectively, or saline) to temporarily inactivate the OFC or DS, or to disconnect the two regions. None of these treatments changed spontaneous locomotion in cocaine-naïve rats. However, both baclofen/muscimol and saline infusions influenced cocaine self-administration behaviour. Infusing baclofen/muscimol or saline into the OFC or into the OFC and contralateral DS decreased responding for cocaine under PR, with baclofen/muscimol and saline having similar effects, except that only OFC-DS disconnection with baclofen/muscimol slowed the pace of cocaine intake. Baclofen/muscimol or saline into the DS also reduced responding for cocaine under PR, but baclofen/muscimol was more effective. We conclude that neuronal activity in the OFC and DS might regulate incentive motivation for cocaine.