NeuropharmacologyShort-acting cocaine and long-acting GBR-12909 both elicit rapid dopamine uptake inhibition following intravenous delivery
Section snippets
Animals
Adult male Sprague–Dawley rats (300–350 g) were housed two per cage on a 12-h light/dark cycle with food and water available ad libitum. All protocols and animal care procedures were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80–23, revised 1996), and approved by the Institutional Animal Care and Use Committee at Wake Forest University Health Sciences. All efforts to minimize the number and suffering of animals
Cocaine produced rapid-onset DA uptake inhibition
To assess the rapidity of cocaine's actions on the DAT, the effects of cocaine on electrically evoked DA uptake and peak height were measured within the NAc of rats receiving a 2 s, i.v. bolus of cocaine (0.75 mg/kg n=8, 1.5 mg/kg n=8, and 3.0 mg/kg n=8) or saline (0.6 ml/kg n=6). Prior to saline or drug administration, electrically evoked DA uptake and peak height parameters were stable and remained at baseline levels following saline injections (uptake, F(1,29)=0.86, P<0.36; peak height, F
Discussion
The current studies demonstrate that i.v. cocaine elicits robust, dose-dependent DA uptake inhibition within 5 s of injection. Maximal levels of uptake inhibition were observed within 30 s of injection and returned to baseline levels in approximately 1 h. This effect of cocaine on DA uptake followed a similar time course to the brain levels of cocaine measured by PET imaging in humans and baboons (Fowler et al 1989, Fowler et al 1998).
Previous neurochemical studies have indicated that i.p.
Acknowledgments
We would like to thank Dr. Evgeny A. Budygin and Joanne K. Konstantopoulos for their expert technical and theoretical advice. This study was supported by P50 DA06634-16 (D.C.S.R.) and R01 DA021325 (S.R.J).
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