Timing of SCH 23390 administration influences extinction of conditioned hyperactivity in mice.

The precise role of the dopamine subtype-1 (D1) receptor in differentially mediating extinction-related processes (memory retrieval vs. memory reconsolidation) in the conditioned hyperactivity paradigm is unknown. Thus, the present experiments determined the effect of a selective D1 receptor antagonist, SCH 23390, on extinction of conditioned hyperactivity when SCH 23390 was administered immediately after (memory reconsolidation; experiment 1) or before (memory retrieval; experiment 2) extinction sessions. Male, Swiss-Webster mice received subcutaneous injections of methamphetamine (1.0 mg/kg) associated with locomotor activity chambers (paired) or in their home cages (unpaired) during the acquisition phase. Following acquisition, paired and unpaired mice received an intraperitoneal injection of either vehicle (physiological saline) or SCH 23390 (0.0125, 0.025, 0.05 mg/kg) immediately after (experiment 1) or received vehicle or SCH 23390 (0.05 mg/kg) 30 min before (experiment 2), daily extinction sessions. Methamphetamine produced robust conditioned hyperactivity, followed by extinction. Furthermore, SCH 23390 (0.05 mg/kg) blocked expression of conditioned hyperactivity, without nonspecifically impairing locomotor activity, when administered before the extinction session, but did not alter the rate of extinction when administered immediately following the sessions. Taken together, these results suggest that the D1 receptor is involved in memory retrieval, but not memory reconsolidation, processes during extinction of conditioned hyperactivity.