Altered cocaine potency in the nucleus accumbens following 7-day withdrawal from intermittent but not continuous treatment: voltammetric assessment of dopamine uptake in the rat.
Using in vitro fast scan cyclic voltammetry, we measured cocaine potency for inhibiting dopamine uptake/clearance in accumbens slices 7 days after withdrawal from chronic cocaine pretreatments. Rats were pretreated with 40 mg/kg per day for 14 days, either via continuous osmotic minipumps or by once-daily injections. The cocaine potency was subsequently assessed for endogenous and exogenous dopamine applied via single-pulse electrical stimulation and caged-dopamine photolysis, respectively. Under baseline conditions, no differences in either endogenous or exogenous dopamine kinetics were observed in the two cocaine pretreatment groups. In contrast, the potency of bath-applied cocaine for inhibiting endogenous dopamine uptake was enhanced in the intermittent injection group with no change in the continuous infusion group. The selective increase in the cocaine potency following injections was also demonstrable for clearance of photo-applied DA. The enhanced cocaine potency in the accumbens slices following 7 days of withdrawal is consistent with the residual sensitization to cocaine-induced locomotion following daily cocaine injections. Behavioral tolerance following continuous infusion, on the other hand, may be mediated via a mechanism distinct from altered dopamine uptake.
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. leedopam@acpub.duke.edu
T H
TH
Lee
K R
KR
Gee
E H
EH
Ellinwood
F J
FJ
Seidler
D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D046508:Culture Techniques; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D003042:Cocaine; D004298:Dopamine