Effects of cocaine and MDMA self-administration on serotonin transporter availability in monkeys.
Although serotonin (5-HT) can interact with dopamine (DA) systems to modulate the subjective and reinforcing effects of psychostimulants such as cocaine and 3,4-methyldioxymethamphetamine (MDMA, ecstasy), the long-term effects of exposure to psychostimulants on brain 5-HT systems are not well characterized. The present study assessed 5-HT transporter (SERT) availability using positron emission tomography (PET) in rhesus monkeys with the SERT-specific radioligand [(11)C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB). SERT availability was assessed in regions of interest including the caudate nucleus, putamen, anterior cingulate cortex, and cerebellum. [(11)C]DASB distribution volume ratios (DVRs) were calculated using the cerebellum as the reference region. DVRs were calculated in control monkeys and in cocaine or MDMA self-administering monkeys approximately 24 h after the last self-administration (SA) session. SERT availability did not differ between monkeys with a history of MDMA SA and control monkeys in any region examined. In contrast, monkeys with a history of cocaine SA showed significantly higher levels of SERT availability in the caudate nucleus and putamen compared to control subjects. These results suggest that chronic SA of cocaine, but not MDMA, leads to alterations in serotonergic function in brain areas relevant to drug abuse. The higher level of SERT availability in cocaine-experienced monkeys may lead to a reduced inhibitory tone of 5-HT on the DA system, which may explain, in part, differences in the abuse liability between cocaine and MDMA.
Banks
Matthew L
ML
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA.
Czoty
Paul W
PW
Gage
H Donald
HD
Bounds
Michael C
MC
Garg
Pradeep K
PK
Garg
Sudha
S
Nader
Michael A
MA
D000818:Animals; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D011859:Radiography; D012646:Self Administration; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*
D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine