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

H. Li, S. Chaney, Michael Forte, J. Hirsh

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

Sensitization to repeated doses of psychostimulants is thought to be an important component underlying the addictive process in humans [1-4]. In all vertebrate animal models, including humans [5], and even in fruit flies, sensitization is observed after repeated exposure to volatilized crack cocaine [6]. In vertebrates, sensitization is thought to be initiated by processes occurring in brain regions that contain dopamine cell bodies [2,7]. 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 (Gα(s)) or inhibitory (Gα(i)) G(α) 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.

Original languageEnglish (US)
Pages (from-to)211-214
Number of pages4
JournalCurrent Biology
Volume10
Issue number4
DOIs
StatePublished - Feb 1 2000

Fingerprint

cocaine
Dopaminergic Neurons
Drosophila melanogaster
dopamine
Cocaine
serotonin
Diptera
Neurons
Dopamine
Serotonin
protein synthesis
neurons
Vertebrates
Brain
Trinitrotoluene
Crack Cocaine
Cell signaling
Tetanus Toxin
Proteins
vertebrates

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Ectopic g-protein expression in dopamine and serotonin neurons blocks cocaine sensitization in Drosophila melanogaster. / Li, H.; Chaney, S.; Forte, Michael; Hirsh, J.

In: Current Biology, Vol. 10, No. 4, 01.02.2000, p. 211-214.

Research output: Contribution to journalArticle

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