Food-reinforced operant behavior in dopamine transporter knockout mice: enhanced resistance to extinction

Dopamine (DA) plays roles in circuits that are important for brain reward and in striatal brain regions that are important for certain types of habit learning. These processes in wildtype, heterozygous, and homozygous dopamine transporter knockout (DAT-KO) mice, which were mildly food deprived and allowed to make nose-poke responses for food reinforcement, were studied. The mice were given 20-min sessions of daily (a) baseline exposure to the operant chambers, (b) acquisition of nose-poke responses in which responses were reinforced under a fixed ratio (FR5) schedule, (c) a progressive ratio schedule in which the number of responses required to obtain food was gradually increased, and (d) extinction of responses in which nose pokes were not followed by food. Neither heterozygous nor homozygous DAT-KO mice differed from their wildtype litter mates in the number of nose pokes displayed during baseline exposures to the chambers, the number of sessions required for acquisition, the number of responses under the FR5 schedule, or the number of responses under the progressive ratio schedule. Interestingly, however, in the five extinction sessions in which food was no longer delivered by nose poking, homozygous DAT-KO mice exerted significantly more responses than mice of either of the other two genotypes. These lines of evidence suggest a greater resistance of DAT-KO mice to the elimination of the response and support roles of dopaminergic systems in habit memory.