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Ectopic G-protein expression in dopamine and serotonin neurons blocks cocaine sensitization in Drosophila melanogaster

journal contribution
posted on 2023-06-08, 09:25 authored by H Li, S Chaney, I J H Roberts, M Forte, J Hirsh
Sensitization to repeated doses of psychostimulants is thought to be an important component underlying the addictive process in humans. In all vertebrate animal models, including humans, and even in fruit flies, sensitization is observed after repeated exposure to volatilized crack cocaine. In vertebrates, sensitization is thought to be initiated by processes occurring in brain regions that contain dopamine cell bodies. Here, we show that modulated cell signaling in the Drosophila dopamine and serotonin neurons plays an essential role in cocaine sensitization. Targeted expression of either a stimulatory (Gas) or inhibitory (Gai) Ga subunit, or tetanus toxin light chain (TNT) in dopamine and serotonin neurons of living flies blocked behavioral sensitization to repeated cocaine exposures. These flies showed alterations in their initial cocaine responsiveness that correlated with compensatory adaptations of postsynaptic receptor sensitivity. Finally, repeated drug stimulation of a nerve cord preparation that is postsynaptic to the brain amine cells failed to induce sensitization, further showing the importance of presynaptic modulation in sensitization.

History

Publication status

  • Published

Journal

Current Biology

ISSN

0960-9822

Publisher

Elsevier

Issue

4

Volume

10

Page range

211-214

Department affiliated with

  • Biology and Environmental Science Publications

Notes

Sussex author mistakenly excluded from original article, correction by journal here: http://dx.doi.org/10.1016/S0960-9822(00)00501-7

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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