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

Abstract

Using slice preparations, we investigated the effects of chronic cocaine treatment on dopamine autoreceptor sensitivity in the nucleus accumbens core. Cocaine (40 mg/kg/day) was given for 14 days, either by continuous subcutaneous infusion (osmotic minipumps) or single daily injections. One or 7 days after cocaine withdrawal, we used fast scan cyclic voltammetry (10 Hz sampling rate) to measure inhibition of electrically evoked dopamine release by quinpirole (3–300 nM). Continuous cocaine infusion increased quinpirole sensitivity on day 1 of withdrawal, particularly at low concentrations of quinpirole, but this effect was no longer evident by day 7. Intermittent cocaine 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 dopamine 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 withdrawal phase.