The purpose of this study was to determine the effects of chronic “binge” administration of cocaine(hourly x 3 ip). Male Fisher rats were treated for 13 days with cocaine(3 x 10 or 15 mg/kg) or saline(3 x 1 mI/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 I 3 days of daily cocaine“binges,” estimated basal dopamine levels were lowered in the ventro-medial stnatum: 10 mg/kg x 3: 3.32±0.52 nM (n= 9) vs. 5.50±1.28 nM (n= 7)(ttest, 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 I 0 mg/kg x 3: 7.1 7±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. 1 0.00±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 stnatum; P<. 05 in the dorsolateral stnatum), 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. These results suggest that chronic binge administration of cocaine significantly lowers basal dopamine levels, and alters the pattern, but not the magnitude, of the response to a reexposure to cocaine.

It is generally accepted that the mesolimbic and mesocortical dopaminergic systems are critical in cocaine-induced euphoria as well as in reinforcing effects ofcocaine. By block-ing DA uptake, cocaine causes a transient increase in DA levels in the synaptic cleft that in turn increases neurotrans-mission in brain reward pathways. Chronic cocaine administration results in compensatory mechanisms of the DA systems, such as decreased DA synthesis(Trulson and Ulis-sey, 1987; Brock et at., 1990) and alterations of DA receptor densities(Peris et at., 1990; Unterwald et at., 1993). Recent in vivo microdialysis studies have reported either no effect or decrease of basal extracellular DA levels(Imperato et at., 1992; Rossetti et al., 1992; Robertson et at., 1991; Parsons et at., 1991; Akimoto et al., 1989; Segal and Kuczenski, 1992; Kalivas and Duffy, 1993) during or after chronic cocaine