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Neuropharmacology. 2004;47 Suppl 1:202-13.

Conditioned reinforcing properties of stimuli paired with self-administered cocaine, heroin or sucrose: implications for the persistence of addictive behaviour.

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Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.


Conditioned environmental stimuli are known to be important determinants of drug seeking. Traditional models of drug seeking under the control of conditioned stimuli have focused on the ability of conditioned reinforcers either to reinstate extinguished responding or to maintain prolonged chains of drug seeking under second-order schedules. These models have consistently suggested that it is the conditioned reinforcing, rather than other, effects of Pavlovian drug stimuli that most profoundly influence drug seeking. However, the impact of drug-associated conditioned reinforcers has not been studied directly and in isolation, not least because the instrumental seeking response is invariably the same as that which was previously reinforced with the drug itself. The purpose of the present study was, therefore, to investigate the conditioned reinforcing properties of drug-paired CSs using an acquisition of a new response procedure in which an animal learns to make a new instrumental response reinforced solely by the CS. It was found that CSs paired with either cocaine, heroin or sucrose supported the rapid acquisition of lever pressing for the CS that persisted over months of repeated, intermittent testing. Furthermore, rats did not acquire the lever press response when the CS was not paired with drug, suggesting that for this stimulus to acquire conditioned reinforcing properties, it must be predictively associated with the drug's effect. Moreover, lever pressing for the CS could not be explained as coincidental to an over-riding Pavlovian approach response to the location of the lever, since animals also acquired discriminated lever pressing when the CS was above the opposite, inactive lever. Extinction decreased responding with conditioned reinforcement, but only when the CS-US association was devalued prior to, and not after, acquisition of the lever press response, providing evidence for the establishment of habitual CS-maintained responding that may explain the persistence of drug-seeking responses in animal models of addiction and relapse.

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