Continuous infusion of selective dopamine uptake inhibitors or cocaine produces time-dependent changes in rat locomotor activity

Chronic continuous cocaine treatment produces a unique pattern of locomotor activation over time. An initial, progressive increase in locomotion is in dicative of sensitization Unlike intermittent cocaine, this increase is sub sequently reversed during the continuous exposure, and activity returns to pre-sensitization levels within days. To study the pharmacological mechanis ms that underlie this phenomenon, osmotic minipumps containing cocaine or s elective uptake inhibitors of dopamine (GBR 12909 or RTI-117), serotonin (f luoxetine), or norepinephrine (nisoxetine) were implanted into rats. Locomo tor activity was measured for 1 h each day, beginning 4 h after pumps were implanted. In the cocaine group, activity was significantly elevated on the first day, peaked between the second and third days, then decreased to a p lateau which remained significantly above control levels through 14 days. P eak activity in the GBR 12909 and RTI-117 animals occurred on the first day , followed by a significant decrease 24-48 h later, but not complete tolera nce. Neither fluoxetine nor nisoxetine altered locomotor activity. The sele ctive dopamine uptake inhibitors produced some of the effects of cocaine. T he possibilities that cocaine interacts with the dopamine transporter in a qualitatively different manner from that of these selective dopamine uptake inhibitors, or that other monoamine systems are involved, are discussed. ( C) 1999 Elsevier Science B.V. Ail rights reserved.