Inhibition of cocaine self-administration by fluoxetine or D-fenfluramine combined with phentermine.
Instrumental responding for intravenous cocaine in rats at 85% of free-feeding weight was significantly decreased 50% by D-fenfluramine plus phentermine (D-Fen/Phen, 5 mg/kg of each for 1 day). A similar effect was obtained in normal-weight rats self-administering a cocaine-heroin mixture. Treating normal-weight animals with fluoxetine (5 mg/kg) for 4 days also significantly decreased cocaine self-administration by half, and then adding phentermine caused an additional decrease in cocaine intake. Animals that were well trained to self-administer drug did not self-administer intravenous D-Fen/Phen or Flu/Phen. The present results confirm that serotonergic drugs can decrease cocaine, or cocaine/heroin, self-administration in rats, and that phentermine adds to the effect. Based on related research with the same dose of D-Fen/Phen, it is suggested that effectiveness in reducing cocaine reinforcement is due in part to a satiating effect in which dopamine and acetylcholine are released in the nucleus accumbens.
Glatz
Andrew C
AC
Department of Psychology, Princeton University, Princeton, NJ 08544, USA.
Ehrlich
Michelle
M
Bae
Richard S
RS
Clarke
Michelle J
MJ
Quinlan
Patricia A
PA
Brown
Emily C
EC
Rada
Pedro
P
Hoebel
Bartley G
BG
D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage* / Q000627:therapeutic use; D016739:Behavior, Addictive / Q000517:prevention & control; D003042:Cocaine / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D005277:Fenfluramine / Q000008:administration & dosage* / Q000627:therapeutic use; D005473:Fluoxetine / Q000008:administration & dosage* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration / Q000706:statistics & numerical data; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use
D001067:Appetite Depressants; D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D005277:Fenfluramine; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors