Loss of alternative non-drug reinforcement induces relapse of cocaine-seeking in rats: role of dopamine D(1) receptors.

Animal models of relapse to drug seeking have focused primarily on relapse induced by exposure to drugs, drug-associated cues or contexts, and foot-shock stress. However, relapse in human drug abusers is often precipitated by loss of alternative non-drug reinforcement. The present experiment used a novel 'resurgence' paradigm to examine relapse to cocaine seeking of rats as a result of loss of an alternative source of non-drug reinforcement. Rats were first trained to press a lever for intravenous infusions of cocaine. Next, cocaine deliveries were omitted and food pellets were provided for an alternative nose-poke response. Once cocaine seeking was reduced to low levels, food pellets for the alternative response were also omitted. Cocaine seeking increased with the loss of the alternative non-drug reinforcer (ie, resurgence occurred) despite continued extinction conditions. The increase in cocaine seeking did not occur in another group of rats injected with SCH 23390 before the loss of the alternative reinforcer. These results suggest that removal of an alternative source of reinforcement may induce relapse of cocaine seeking and that the dopamine D(1) receptor may have a role in this effect.