Prolonged daily exposure to i.v. cocaine results in tolerance to its stimulant effects.

We have previously shown that 1 h, but not 6 h, of daily access to i.v. cocaine induces a sensitized response to i.v. cocaine challenge after 14 days of withdrawal. Here we tried to replicate these results using an i.p. cocaine challenge and adding a group of animals that had 1 h daily access to cocaine, but maintained levels of administration comparable to that of saline animals (i.e. a Coc group). Since addiction-associated neuroadaptations are particularly long lasting, we also tested the response to cocaine challenge after a longer withdrawal period of 60 days. Rats had daily access to i.v. self-administered saline or cocaine for 1 h (Coc1h), or to cocaine for 6 h (Coc6h) over 8 days. Subsequently, after 14 days of withdrawal only Coc animals showed a sensitized locomotor response to cocaine challenge administered i.p. After 60 days of withdrawal, i.p. cocaine failed to produce a sensitized response in Coc1h animals and produced a tolerant response in Coc6h animals. The present data support the notion that 6 h of daily access to cocaine leads to different neuroadaptations than those resulting from 1 h of daily access to the drug. In addition, these data further demonstrate a dissociation between sensitization and addiction to cocaine.