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Drug discrimination and neurochemical studies in alpha 7 null mutant mice: tests for the role of nicotinic alpha 7 receptors in dopamine release


Reference:

Quarta, D., Naylor, C. G., Barik, J., Fernandes, C., Wonnacott, S. and Stolerman, I. P., 2009. Drug discrimination and neurochemical studies in alpha 7 null mutant mice: tests for the role of nicotinic alpha 7 receptors in dopamine release. Psychopharmacology, 203 (2), pp. 399-410.

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Official URL:

http://dx.doi.org/10.1007/s00213-008-1281-x

Abstract

The nicotine discriminative stimulus has been linked to beta 2-containing (beta 2*) nicotinic receptors, with little evidence of a role for alpha 7 nicotinic receptors, because nicotine discrimination was very weak in beta 2 null mutant mice but normal in alpha 7 mutants. As both alpha 7 and beta 2* nicotinic receptors have been implicated in nicotine-stimulated dopamine overflow, this study focused on the dopamine-mediated element in the nicotine stimulus by examining cross-generalisation between amphetamine and nicotine. Male alpha 7 nicotinic receptor null mutant mice and wild-type controls were bred in-house and trained to discriminate nicotine (0.8 mg/kg) or (+)-amphetamine (0.6 mg/kg) from saline in a two-lever procedure with a tandem VI-30 FR-10 schedule of food reinforcement. Dopamine release from striatal slices was determined in parallel experiments. An alpha 7 nicotinic receptor-mediated component of dopamine release was demonstrated in tissue from wild-type mice using choline as a selective agonist. This response was absent in tissue from null mutant animals. The mutation did not influence acquisition of drug discriminations but subtly affected the results of cross-generalisation tests. In mice trained to discriminate nicotine or amphetamine, there was partial cross-generalisation in wild-type mice and, at certain doses, these effects were attenuated in mutants. Further support for an alpha 7 nicotinic receptor-mediated component was provided by the ability of the alpha 7 nicotinic receptor antagonist methyllycaconitine to attenuate responses to nicotine and amphetamine in wild-type mice. These findings support the concept of an alpha 7 nicotinic receptor-mediated dopaminergic element in nicotine discrimination, warranting further tests with selective dopamine agonists.

Details

Item Type Articles
CreatorsQuarta, D., Naylor, C. G., Barik, J., Fernandes, C., Wonnacott, S. and Stolerman, I. P.
DOI10.1007/s00213-008-1281-x
Uncontrolled Keywordsacetylcholine receptor, nicotinic receptors, methyllycaconitine, drug discrimination, behaviour, mice, release, dopamine, monoamine, nicotine, amphetamine, binding, dopamine release
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code13923

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