PHARMACOGENETICS OF COCAINE .1. LOCOMOTOR-ACTIVITY AND SELF-SELECTION

We investigated the effects of cocaine on multiple activity measures a nd cocaine self-selection in C57BL/6Ibg(dagger) and DBA/2Ibg mice. Mal e mice were tested in an automated activity monitor at three doses of cocaine, 5.15 and 30 mg kg-1. Activity measures included locomotion, r earings, stereotyped movements and wall-seeking. Testing was conducted on 2 days with saline injection, i.p. on day one and cocaine i.p. inj ected on day two. We also tested other mice of both strains for cocain e ingestion in a two-choice test, pairing tap water with 40 mg% cocain e HCI in tap water. Two separate groups of mice received 15 or 30 mg k g-1 of cocaine i.p., killed at 5 min and brain cocaine levels were det ermined by HPLC. Cocaine produced dose-related increases in locomotion in both strains, with a delay in initial activation noticed at 30 mg kg-1 in C57s but not in DBAs. In DBAs, cocaine suppressed rearings and increased stereotyped movements while having no consistent effect on either behaviour in C57s. At all doses, cocaine produced moderate incr eases in proximity to the wall in DBAs and 30 mg kg-1 produced pronoun ced wall-seeking in C57s. At 15 and 30 mg kg-1 DBAs tended to have hig her levels of cocaine in whole brain than did C57s. Finally, C57s cons umed significantly more cocaine than did the DBAs.