Altered sensitivity of dopamine autoreceptors in rat accumbens 1 and 7 days after intermittent or continuous cocaine withdrawal

Using slice preparations, we investigated the effects of chronic cocaine tr eatment on dopamine autoreceptor sensitivity in the nucleus accumbens core. Cocaine (40 mg/kg/day) was given for 14 days, either by continuous subcuta neous infusion (osmotic minipumps) or single daily injections. One or 7 day s after cocaine withdrawal, we used fast scan cyclic voltammetry (10 Hz sam pling rate) to measure inhibition of electrically evoked dopamine release b y quinpirole (3-300 nM), Continuous cocaine infusion increased quinpirole s ensitivity on day 1 of withdrawal, particularly at low concentrations of qu inpirole, but this effect was no longer evident by day 7, Intermittent coca ine injections had no effect on day 1 of withdrawal but by day 7 there was a quinpirole subsensitivity. On either withdrawal day, the baseline peak do pamine release or uptake half-life exhibited no treatment group differences , It is suggested that these cocaine dosing regimes cause differential and dynamic changes in dopamine autoreceptor sensitivity during the early withd rawal phase. (C) 2000 Elsevier Science Inc.