Selegiline potentiates cocaine-induced increases in rodent nucleus accumbens dopamine.
Selegiline has been proposed as a treatment for cocaine addiction and studies in humans suggest that it attenuates cocaine's reinforcing effects. Here we assessed the effects of selegiline treatment on cocaine-induced increases in nucleus accumbens (NAc) dopamine (DA) in freely moving rodents. Chronic treatment with selegiline (L-deprenyl, 0.25/mg/kg, 24 days) potentiated cocaine-induced increases in NAc DA from 350-600%. However, this enhanced response was abolished when animals were treated chronically with both cocaine and selegiline. Inasmuch as increases in NAc DA are associated with the reinforcing effects of cocaine, these results obtained in rodents suggest that MAO-A and -B inhibition may not be a suitable strategy to antagonize cocaine's reinforcing effects during cocaine detoxification. On the other hand, chronic selegiline treatment may improve DA deficits, which are thought to contribute to relapse through a decreased response to natural rewards.
Schiffer
Wynne K
WK
Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York 11794, USA. wynne@bnl.gov
Azmoodeh
Manijeh
M
Gerasimov
Madina
M
Volkow
Nora D
ND
Fowler
Joanna S
JS
Dewey
Stephen L
SL
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D008297:Male; D017551:Microdialysis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D018696:Neuroprotective Agents; D012642:Selegiline; D003042:Cocaine; D004298:Dopamine