Potentiation of DOM-induced stimulus control by fluoxetine and citalopram: role of pharmacokinetics.
The present investigation examined the interaction between 2,5-dimethoxy-4-methylamphetamine [DOM] and the selective serotonin reuptake inhibitor [SSRI] citalopram in rats trained with DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. Pretreatment with citalopram at a dose of 1.0 mg/kg shifted the DOM dose response relationship to the left. Unlike previously tested SSRI's, the enhancement of DOM-induced stimulus control occurred in the absence of significant partial substitution by citalopram. DOM brain levels were measured using a GC-MS method both in the presence and absence of citalopram and fluoxetine in order to evaluate the pharmacokinetic contribution to the observed behavioral effect. The data indicated that fluoxetine but not citalopram significantly increased DOM brain levels. It is concluded that the effects of DOM as a discriminative stimulus are potentiated by the acute administration of citalopram and this effect is not mediated by additivity or pharmacokinetic mechanisms.
Eckler
J R
JR
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA. eckler@buffalo.edu
Doat
M M
MM
Rabin
R A
RA
Winter
J C
JC
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D005473:Fluoxetine / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012054:Reinforcement, Psychology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D015283:Citalopram; D005473:Fluoxetine; D006213:Hallucinogens; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors