Associational and nonassociational mechanisms in locomotor sensitization to the dopamine agonist quinpirole.

A pairing paradigm was employed to explore the contribution of associational mechanisms to the expression of sensitization to the dopamine agonist quinpirole. Rats received ten quinpirole injections in the test environment (Group Paired) or in the home cage (Group Unpaired), and saline in the alternate environment. A third group received saline injections in both environments (Group Acute). Subjects received quinpirole on the 11th injection as a test for locomotor sensitization, and saline on the next injection as a test for conditioned activity. The range of discriminative stimuli predicting a drug versus a non-drug injection was increased across three independent experiments in an effort to detect a possible associational effect. Regardless of the strength of discriminative stimuli, both Paired and Unpaired groups showed locomotor sensitization to 0.5 mg/kg quinpirole compared with the Acute group. However, the Paired group showed more locomotion than the Unpaired group in the last minutes of the sensitization test. With a lower sensitizing dose of quinpirole (0.1 mg/kg) used in one experiment, only the Paired group showed locomotor sensitization. For both doses, the Paired, but not the Unpaired groups showed conditioned locomotion. It is suggested that with moderate doses of quinpirole, expression of locomotor sensitization does not require drug-signalling cues though such signals may have a modulatory influence. With lower quinpirole doses, however, quinpirole sensitization is context-dependent.