Role of the dopamine transporter and the sodium channel in the cocaine-like discriminative stimulus effects of local anesthetics in rats

Psychopharmacology
K M WilcoxW L Woolverton

Abstract

Local anesthetics bind to the dopamine transporter (DAT), inhibit dopamine (DA) uptake and have been reported to have cocaine-like discriminative stimulus effects. The hypothesis of the present study was that affinity at the DAT and potency as a DA uptake blocker determines potency as a cocaine-like discriminative stimulus among local anesthetics, and maximum DA uptake inhibition determines maximum cocaine-like discriminative stimulus effects. Cocaine-like discriminative potency was compared to DAT affinity and DA uptake inhibition potency, and maximum cocaine-like discriminative stimulus effects were compared to maximum DA uptake inhibition for procaine, chloroprocaine, dimethocaine, tetracaine and lidocaine. Discriminative stimulus effects were determined in two groups of rats using 10 mg/kg and 3.0 mg/kg cocaine training doses. DAT affinity and DA uptake inhibition effects were determined in vitro in rat caudate nucleus tissue. Additionally, sodium channel affinity was determined in rat frontal cortex tissue. In the 10 mg/kg group, none of the local anesthetics fully substituted for cocaine and all decreased response rate. Rate decreasing potencies were positively correlated with sodium channel affinities. In the low trainin...Continue Reading

Citations

Nov 27, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Eugene A Kiyatkin, Michael S Smirnov
Aug 3, 2011·Behavioural Pharmacology·Ian P StolermanKathleen A Grant
Dec 16, 2006·Neuroscience Letters·Zhixia WangWilliam Woolverton
Dec 13, 2006·The European Journal of Neuroscience·Nina C Di PietroKathleen M Kantak
Aug 26, 2006·The European Journal of Neuroscience·P Leon Brown, Eugene A Kiyatkin

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