Enhanced conditioned approach responses in transgenic mice with impaired glucocorticoid receptor function.

The long-term consequences of impaired glucocorticoid receptor (GR) function on reward-related learning were studied in transgenic mice with impaired GR function in a series of experiments taxing conditioned and unconditioned approach responses to stimuli predictive of food. There was a double-dissociation in that transgenic mice with impaired GR activity showed enhanced conditioned exploration in situations when stimuli predicted reward, while free-feeding food consumption over 24 h was reduced. Previous experiments have shown altered accumbens dopaminergic activity in these animals. In line with these findings, we observed an enhanced behavioural stimulation of transgenic mice following administration of d-amphetamine (2 mg/kg). This suggests that the increase in preparatory responses in transgenic mice may be mediated via an enhanced accumbens dopaminergic activity, possibly secondary to alterations in other brain systems.