Presynaptic stimulation and development of locomotor sensitization to the dopamine agonist quinpirole

To assess whether locomotor sensitization induced by repeated injections of the dopamine agonist quinpirole reflects tolerance of the drug's presynaptic depressive effects on locomotion, independent groups of rats were treated chronically (every 3 daysx10) with either a presynaptic dose of quinpirole (0.025 mg/kg; n=27), a postsynaptic dose (0.5 mg/kg; n=27), or saline (n=26). Following chronic treatment, a full dose-response profile was determined to assess the presence of sensitization. Results indicated that treatment with the postsynaptic, but not the presynaptic, dose of quinpirole induced locomotor sensitization. Moreover, chronic treatment with low-dose quinpirole did not yield tolerance of the drug's depressive effects. It is suggested that presynaptic dopamine receptors may require extensive spatial and/or temporal summation to become tolerant.