The purpose of this study was to determine the effects of chronic "binge" administration of cocaine (hourly x 3 i.p.). Male Fisher rats were treated for 13 days with cocaine (3 x 10 or 15 mg/kg) or saline (3 x 1 ml/kg). On day 14, microdialysis was performed on the rats and all received cocaine (3 x 10 or 15 mg/kg). Dialysate samples were collected from the ventromedial (nucleus accumbens and immediate surrounding striatum) and dorsolateral striata. After 13 days of daily cocaine "binges," estimated basal dopamine levels were lowered in the ventromedial striatum: 10 mg/kg x 3: 3.32 +/- 0.52 nM (n = 9) vs. 5.50 +/- 1.28 nM (n = 7) (t test, P < .1), and 15 mg/kg x 3: 3.50 +/- 0.37 nM (n = 6) vs. 5.66 +/- 0.58 nM (n = 7) (P < .01); and in the dorsolateral striatum 10 mg/kg x 3: 7.17 +/- 0.55 nM (n = 9) vs. 9.54 +/- 1.08 nM (n = 7) (t test, P < .05), and 15 mg/kg x 3: 6.88 +/- 0.22 nM (n = 5) vs. 10.00 +/- 1.04 nM (n = 7) (t test, P < .03). In cocaine-pretreated animals the cocaine "binge" on day 14 resulted in a lower elevation in extracellular DA levels than their corresponding values in saline-pretreated animals (pretreatment effect, P < .04 in the ventromedial striatum; P < .05 in the dorsolateral striatum), although the percent increases over baseline were of similar magnitude. In addition, the acute tolerance phenomenon observed during an initial cocaine binge was abolished after chronic exposure.(ABSTRACT TRUNCATED AT 250 WORDS)