Nicotine Indirectly Inhibits [³H]Dopamine Uptake at Concentrations That Do Not Directly Promote [³H]Dopamine Release in Rat Striatum

Abstract

The effects of both (-)- and (+)-nicotine isomers were examined on in vitro uptake and release of [3H]dopamine in rat striatum. Both isomers inhibited uptake of [3H]dopamine in chopped tissue at concentrations well below those necessary for promoting release of preloaded [3H]dopamine. (-)-Nicotine was more potent than (+)-nicotine both at inhibiting uptake and at promoting release. Unlike other dopamine uptake inhibitors, however, nicotine inhibited only 50% of the total uptake. In the presence of 1 nM nicotine, the residual [3H]dopamine uptake was less sensitive to inhibition by cocaine than uptake in the absence of nicotine. Nicotine did not compete against the binding of [3H]GBR 12935, a selective dopamine uptake inhibitor. The nicotinic receptor agonists carbachol and 1,1-dimethyl-4-phenylpiperazinium iodide also inhibited uptake, whereas the nicotinic antagonists chlorisondamine and mecamylamine blocked nicotine's effect. Thus, the effect of nicotine on dopamine uptake appears to be mediated by a receptor similar to the nicotinic acetylcholine receptor. These receptors do not seem to be on the terminals that are accumulating dopamine, however, since tetrodotoxin prevented the effect of nicotine on [3H]dopamine uptake and nicotine had no effect on uptake in a synaptosomal preparation.

Nicotinic Receptor Modulation of Dopamine Transporter Function in Rat Striatum and Medial Prefrontal Cortex

“…Surprisingly, nicotine (0.4 mg/kg) has been reported to increase DA clearance (enhance DAT function) in the nucleus accumbens in anesthetized rats (Hart and Ksir, 1996). The latter results also contrast findings in vitro in which nicotine and another nicotinic agonist, 1,1-dimethyl-4-phenyl-piperazinium, have been reported to decrease [ 3 H]DA uptake into chopped striatum and PC12 cells, respectively (Izenwasser et al, 1991;Huang et al, 1999). However, these in vitro findings have not been replicated (Carr et al, 1989;Kramer et al, 1989;Rowell and Hill 1993;Zhu et al, 2004).…”

Blockade of nicotinic receptor‐mediated release of dopamine from striatal synaptosomes by chlorisondamine and other nicotinic antagonists administered in vitro

“…n* Chesselet et al, 1979;Westfall et al, 1987;Izenwasser et al, 1991). Two mechanisms of action have been identified.…”

“…This phenomenon has been repeatedly described in the nigrostriatal dopaminergic system, where micromolar concentrations of nicotine stimulate the release of dopamine in a receptormediated manner, both in vitro (Giorguieff et al, 1976;1977;Giorguieff Chesselet et al, 1979;Westfall et al, 1987;Rapier et al, 1988;Rowell & Wonnacott, 1990;Izenwasser et al, 1991;Grady et al, 1992) and in vivo (Giorguieff et al, 1976;Imperato et al, 1986). Thus, the ability of nicotine to promote dopamine release from striatal synaptosomes provides a reliable in vitro assay for CNS nicotinic receptor function.…”

“…Reports of central blockade by CHL have relied almost exclusively on behavioural measures that reflect central actions of nicotine. However, two recent in vitro studies reported that CHL abolished nicotine-induced inhibition of dopamine uptake in striatal tissue slices (Izenwasser et al, 1991) and nicotine-induced rubidium efflux from mouse striatal synaptosomes (Marks et al, 1993 (Schwartz et al, 1982;Clarke et al, 1984) suggests that this antagonist does not act at the agonist recognition site(s) situated on the nicotinic receptor macro-'Author for correspondence. molecule.…”

The pharmacology of the nicotinic antagonist, chlorisondamine, investigated in rat brain and autonomic ganglion

“…Although there is in vitro evidence that chlorisondamine blocks CNS nicotinic receptors acutely (Izenwasser et al, 1991;Marks et al, 1993;El-Bizri & Clarke, 1994a), the mechanism underlying its long-term blocking action is not understood.…”