Title

Nicotinic receptor-mediated regulation of the dopamine transporter in rat prefrontocortical slices following chronic in vivo administration of nicotine

Document Type

Journal Article

Publication Date

12-1-2003

Journal

Schizophrenia Research

Volume

65

Issue

1

DOI

10.1016/S0920-9964(02)00500-5

Keywords

Chronic nicotine treatment; Dopamine release; Dopamine transporter; Nicotine; Schizophrenia

Abstract

Low levels of dopaminergic activity in prefrontal cortex are thought to contribute to negative symptoms of schizophrenia. Negative symptoms are associated with the prefrontocortical area of the brain. Schizophrenic patients have a high rate of smoking, which by subjective as well as objective measures produces a cognitive benefit. We have previously shown that agonists at nicotinic receptors containing α4 and β2 subunits can enhance amphetamine-stimulated [3H]dopamine ([3H]DA) release via the dopamine transporter (DAT) from slices of rat prefrontal cortex. This effect is selective for prefrontal cortex; the enhancement does not occur in striatum or nucleus accumbens. The enhancement is dependent upon activation of protein kinase C (PKC). In the current study, we show that the enhancement of amphetamine-stimulated [3H]DA release is maintained after 10 days of chronic nicotine treatment, delivered subcutaneously twice daily. There are no significant changes in the ability of prefrontocortical brain slices to take up [3H]DA in tissue prepared from nicotine-treated vs. saline-treated rats. Nicotinic receptors mediating enhancement of amphetamine-stimulated [ 3H]DA release are at least partially localized to nerve terminals, as an enhancement in release is also observed in synaptosomal preparations. Finally, the sensitivity of the nicotine enhancement in release to the PKC inhibitor chelerythrine is also seen in synaptosomal preparations, suggesting that the signaling mechanism activated through α4β2 receptors is intact. © 2003 Elsevier Science B.V. All rights reserved.

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