Role of serotonin in cocaine effects in mice with reduced dopamine transporter function.
The mesolimbic dopaminergic system, especially the nucleus accumbens, has received attention for its involvement in the reinforcing and addictive properties of cocaine and other drugs of abuse. It is generally accepted that the ability of cocaine to inhibit the dopamine transporter (DAT) is directly related to its reinforcing actions. However, mice with a genetic deletion of the DAT (DAT-KO mice) still experience the rewarding effects of cocaine. These behavioral findings suggest that there is an alternate site for cocaine reinforcement. We demonstrate here that modulation of the serotonergic system in the ventral tegmental area, where the mesolimbic dopamine system originates, is a target of cocaine action. The ultimate effect of this serotonin mechanism in animal models with sustained elevations of dopamine may be a feed-forward enhancement of dopamine levels in the nucleus accumbens.
Mateo
Yolanda
Y
Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Budygin
Evgeny A
EA
John
Carrie E
CE
Jones
Sara R
SR
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D004298:Dopamine / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins; D005473:Fluoxetine / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D012054:Reinforcement, Psychology; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000503:physiopathology
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493215:Slc6a3 protein, mouse; C493231:Slc6a4 protein, mouse; D005473:Fluoxetine; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine