Nicotinic receptor-mediated regulation of dopamine transporter activity in rat prefrontal cortex
Amphetamine; Epibatidine; Facilitated exchange diffusion; Nicotine; Schizophrenia
The objective of this study was to determine whether nicotine could selectively influence dopamine levels in the prefrontal cortex as compared with other dopaminergic areas of brain. Using a superfusion system, we found that nicotine and other agonists at nicotinic acetylcholine receptors enhanced the release of radiolabeled dopamine that was stimulated by 10 μM amphetamine from slices prepared from rat prefrontal cortex. In contrast, nicotine had no effect on amphetamine-stimulated [3H]dopamine release from slices of nucleus accumbens nor striatum. Under the conditions used, which included no added calcium to exclude contribution by exocytotic release, nicotine had no effect on basal release of [3H]dopamine. The enhancement by nicotine was concentration-dependent, reaching a maximum at 5 μM, and producing less release at higher concentrations. Enhancement by nicotine was fully reversed by 30 μM dihydro-β-erythroidine, and by 10 μM mecamylamine, but was not affected by α-bungarotoxin. The potencies of nicotine, epibatidine, cytisine, and A85380 to enhance amphetamine-stimulated dopamine release, as well as the sensitivity of nicotine enhanced release to antagonists, are consistent with mediation via a high-affinity nicotinic acetylcholine receptor containing α4 and β2 subunits, the major species of nicotinic receptor in forebrain. Since low dopaminergic activity in prefrontal cortex is correlated with cognitive deficits in schizophrenia, our findings may help explain why these deficits are improved in schizophrenics by smoking or nicotine administration. (C) 2000 Wiley-Liss, Inc.
Drew, A., Derbez, A., & Werling, L. (2000). Nicotinic receptor-mediated regulation of dopamine transporter activity in rat prefrontal cortex. Synapse, 38 (1). http://dx.doi.org/10.1002/1098-2396(200010)38:1<10::AID-SYN2>3.0.CO;2-T