The activation of extracellular signal-regulated kinase protein (ERK) has been linked to the adaptive responses to environmental changes and memory. The aim of this study was to measure ERK activation in primary dopamine projection areas namely, the prefrontal cortex and the nucleus accumbens, following a conditioned dopaminergic drug response. Initially, the effect of unconditioned apomorphine (2.0 mg/kg) administration on ERK activation was measured and the results showed an increase in ERK for both brain regions. Subsequently, two experiments were conducted to assess ERK activation in these two areas following apomorphine conditioned contextual stimuli. In experiment 1, rats received 5 daily injections of 2.0 mg/kg apomorphine or vehicle immediately prior to placement in an open-field. After a withdrawal period of two days, a conditioning test was conducted, in which rats received a 30 min non-drug test. Immediately after completion of the test, an immunohistochemical protocol was carried out to measure ERK activation. In experiment 2, a similar test protocol was performed except that the treatments were administered 30 min following open-field tests (post-trial experiment). The results showed that the repeated apomorphine treatments given prior to testing induced conditioned effects. An increase in ERK activation was seen in the prefrontal cortex but not in the nucleus accumbens. There was no conditioning response observed in the post-trial experiment and no differential ERK activation. These observations implicate the prefrontal cortex in the associative neuro-adaptive changes induced by dopaminergic stimulation.