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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 HirshSensitization 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 BiologyISSN
0960-9822Publisher
ElsevierExternal DOI
Issue
4Volume
10Page range
211-214Department 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)00501-7Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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