Sensitization to apomorphine-induced rotational behavior in 6-OHDA-lesioned rats: effects of NMDA antagonists on drug...

The development of drug-induced behavioral sensitization is thought to underlie many of the motor complications that accompany chronic L-DOPA treatment of patients with Parkinson's disease. As the development of sensitization to some dopaminergic behaviors has been linked to alterations in NMDA neurotransmission in animal models, we sought to determine whether or not NMDA antagonists can block the development of sensitization to rotational effects of dopamine agonists in rodents with unilateral nigrostriatal lesions. Rats with unilateral 6-hydroxydopamine lesions received either a single dose or eight daily doses of apomorphine, each dose preceded by the NMDA antagonists MK-801 or CPP. Three days after the last apomorphine dose, the circling behavior produced by the D1 agonist SKF 38393 was measured. A single dose of MK-801 (0.1 mg/kg) prevented the subsequent response to SKF 38393 but neither repeated treatment with MK-801 (0.1 or 0.3 mg/kg) nor CPP (0.1 mg/kg) preceding apomorphine prevented the subsequent response to SKF 38393 or attenuated the response in comparison to a control group. Each of the chronic treatment groups exhibited an increase in rotational effects of apomorphine despite MK-801 or CPP pretreatment. These data suggest behavioral sensitization in unilateral nigrostriatally lesioned rats chronically treated with apomorphine is not dependent upon stimulation of NMDA receptors.