Acute tolerance to the dopamine response induced by a binge pattern of cocaine administration in male rats: an in vivo microdialysis study.

To address a growing concern about the relevance of the pattern of cocaine administration used in animal studies, the aim of the present work was to establish the dopamine (DA) response of an acute cocaine "binge" that attempts to parallel as closely as possible the human drug abuse pattern. For this purpose, cocaine (10 or 15 mg/kg, i.p.) was administered three or five times at 1-hr intervals in the beginning of the resting period of the rat's light/dark cycle. Extracellular DA levels were measured in the ventromedial (nucleus accumbens and immediately surrounding striatum) and dorsolateral striata using an in vivo microdialysis technique coupled with high-performance liquid chromatography. In addition, extracellular cocaine levels were measured in the dorsolateral striatum. In the ventromedial striatum, acute "binge" administration of cocaine resulted in an increase in extracellular DA levels that plateaued after the first or second injection. This plateau effect persisted even after the cocaine dose or the number of injections was increased. In the dorsolateral striatum, a plateau in extracellular DA levels was found in the three consecutive 10-mg/kg cocaine injection series. This plateau was found in spite of the significant accumulation of extracellular cocaine from one injection to the next. However, increasing the dose or number of injections led to an increasing elevation of DA levels. Thus a decrease in DA responsivity to repeated cocaine was observed in both regions, although this tolerance was more pronounced in the ventromedial striatum.