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Reduced Clearance of Exogenous Dopamine in Rat Nucleus Accumbens, but Not in Dorsal Striatum, Following Cocaine Challenge in Rats Withdrawn from Repeated Cocaine Administration
Author(s) -
Cass Wayne A.,
Gerhardt Greg A.,
Gillespie Kelly,
Curella Pamela,
Mayfield R. Dayne,
Zahniser Nancy R.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03565.x
Subject(s) - nucleus accumbens , dopamine , dopamine transporter , striatum , chemistry , saline , catecholamine , medicine , dopamine plasma membrane transport proteins , endocrinology , mesolimbic pathway , anesthesia , dopamine uptake inhibitors , pharmacology , dopaminergic , ventral tegmental area
We investigated whether changes in the dopamine transporter in the nucleus accumbens or striatum are involved in cocaine‐induced behavioral sensitization by using in vivo electrochemistry to monitor the clearance of locally applied dopamine in anesthetized rats. Rats were injected with cocaine‐HCI (10 mg/kg i.p.) or saline daily for 7 consecutive days and then withdrawn for 7 days. Pressure ejection of a finite amount of dopamine at 5‐min intervals from a micropipette adjacent to the electrochemical recording electrode produced transient and reproducible dopamine signals. After a challenge injection of cocaine (10 mg/kg i.p.), the signals in the nucleus accumbens of cocaine‐treated animals became prolonged and the clearance rate of the dopamine decreased, indicating significant inhibition of the dopamine transporter. In contrast, simultaneous measurements in the dorsal striatum indicated a transient increase in both the amplitude of the signals and the clearance rate of the dopamine. The signals in both brain regions in the saline‐treated animals given the cocaine challenge were similar to those in untreated animals given an acute injection of cocaine (10 mg/ kg i.p.) or saline. Behaviorally, not all of the cocaine‐ treated animals were sensitized; however, both sensitized and nonsensitized animals displayed similar changes in dopamine clearance rate. Quantitative autoradiography with [ 3 H]mazindol revealed that the affinity of the dopamine transporter for cocaine and the density of binding sites were similar in cocaine‐ and saline‐treated rats. The decrease in dopamine clearance rate observed in the nucleus accumbens of the cocaine‐treated rats after a challenge injection of cocaine is consistent with increased do‐ paminergic transmission, but does not appear to be sufficient in itself for producing behavioral sensitization.