Tetrodotoxin-sensitivity of nicotine-evoked dopamine release from rat striatum

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Abstract

Recent observations from synaptosome preparations have questioned the tetrodotoxin (TTX) insensitivity of nicotine-evoked dopamine release in the striatum, a characteristic previously considered diagnostic of presynaptically located nicotinic acetylcholine receptors (nAChRs). Therefore, we have undertaken a comparison of nicotine-evoked dopamine release in the presence of TTX from the rat striatum in vitro, using synaptosomes and brain slices, and in vivo, using microdialysis. In P2 and Percoll-purified synaptosome preparations, 1.5 μM TTX partially inhibited nicotine-evoked [3H]dopamine release by 54% and 37%, respectively, whereas in more intact preparations (brain slices and microdialysis) TTX completely inhibited mecamylamine-sensitive nicotine-stimulated dopamine release. These results suggest that caution should be exercised in the interpretation of TTX sensitivity of nicotine-evoked responses with regard to the location of nAChRs.

Section snippets

Synaptosomes and slices

Male Sprague–Dawley rats (240–280 g, University of Bath breeding colony) were killed by cervical dislocation, decapitated and brain striata rapidly dissected for preparing synaptosomes or slices. P2 synaptosome fractions were prepared as described previously (Soliakov et al., 1995). Percoll gradient purified synaptosomes (fraction 4) were prepared according to the procedure of Dunkley et al. (1988)as previously described by Soliakov and Wonnacott (1996). Synaptosomes were loaded with [3

Results

The first experiments compared the TTX sensitivity of nicotine-evoked [3H]dopamine release from crude P2 synaptosomes and from a purer preparation, isolated on Percoll gradients (Fig. 1(A, B), respectively). In both cases 10 μM nicotine (a concentration that is just maximally effective in striatal synaptosome preparations (Whiteaker et al., 1995)) evoked the release of [3H]dopamine, and this was inhibited by 20 μM mecamylamine, to 23±2% (n=3) of control for P2 synaptosomes and 29±8% (n=4) of

Discussion

The object of this study was to characterise the TTX-sensitivity of nicotine-stimulated dopamine release from rat striatum in superfused synaptosomes, superfused slices and by in vivo microdialysis.

Figures 1 and 2 show that TTX can inhibit nicotine-evoked dopamine release in all three experimental preparations, but to varying degrees. This is unlikely to reflect a direct interaction of TTX with the nAChR because (i) nicotine or anatoxin-a-evoked and veratridine-evoked responses are similarly

Acknowledgements

This study was supported by grants from The Wellcome Trust (038960, to P.H.R. and S.W.) and BBSRC (to S.W.).

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