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 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.
Davidson
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Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
Ellinwood
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Lee
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D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology
D011954:Receptors, Dopamine; D019257:Quinpirole; D003042:Cocaine; D004298:Dopamine