Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Science ; 373(6560): 1252-1256, 2021 Sep 10.
Article in English | MEDLINE | ID: mdl-34516792

ABSTRACT

Compulsive drug use despite adverse consequences defines addiction. While mesolimbic dopamine signaling is sufficient to drive compulsion, psychostimulants such as cocaine also boost extracellular serotonin (5-HT) by inhibiting reuptake. We used SERT Met172 knockin (SertKI) mice carrying a transporter that no longer binds cocaine to abolish 5-HT transients during drug self-administration. SertKI mice showed an enhanced transition to compulsion. Conversely, pharmacologically elevating 5-HT reversed the inherently high rate of compulsion transition with optogenetic dopamine self-stimulation. The bidirectional effect on behavior is explained by presynaptic depression of orbitofrontal cortex­to­dorsal striatum synapses induced by 5-HT via 5-HT1B receptors. Consequently, in projection-specific 5-HT1B receptor knockout mice, the fraction of individuals compulsively self-administering cocaine was elevated.


Subject(s)
Cocaine-Related Disorders/metabolism , Receptor, Serotonin, 5-HT1B/metabolism , Serotonin/metabolism , Synaptic Transmission , Animals , Cocaine/administration & dosage , Cocaine-Related Disorders/genetics , Dopamine/metabolism , Gene Knock-In Techniques , Mice , Mice, Knockout , Optogenetics , Receptor, Serotonin, 5-HT1B/deficiency , Serotonin Plasma Membrane Transport Proteins/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...