Serotonergic/glutamatergic interactions: potentiation of phencyclidine-induced stimulus control by citalopram.
Previous investigations in our laboratory have found that the stimulus effects of the hallucinogenic serotonergic agonists DOM and LSD are potentiated by phencyclidine [PCP], a non-competitive NMDA antagonist. Also suggestive of behaviorally significant serotonergic/glutamatergic interactions is our finding that stimulus control by both PCP and LSD is partially antagonized by the mGlu2/3 agonist, LY 379268. These observations coupled with the fact that the stimulus effects of LSD and DOM are potentiated by selective serotonin reuptake inhibitors [SSRIs] led us in the present investigation to test the hypothesis that stimulus control by PCP is potentiated by the SSRI, citalopram. Stimulus control was established with PCP [3.0 mg/kg; 30 min pretreatment time] in a group of 12 rats. A two-lever, fixed ratio 10, positively reinforced task with saline controls was employed. Potentiation by citalopram of an intermediate dose of PCP was observed. In an attempt to establish the mechanism by which citalopram might interact with PCP, subsequent experiments examined the effects on that interaction of antagonists at serotonergic receptors. It was found that the selective 5-HT2C-selective antagonists, SDZ SER 082 and SB 242084, significantly, albeit only partially, blocked the effects of citalopram on PCP. In agreement with our previous conclusions regarding the interaction of citalopram with DOM, the present data suggest that potentiation of the stimulus effects of PCP by citalopram are mediated in part by agonist activity at 5-HT2C receptors.
Winter
J C
JC
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, 102 Farber Hall, State University of New York at Buffalo, Buffalo, NY 14214-3000, USA. jcwinter@buffalo.edu
Eckler
J R
JR
Rice
K C
KC
Rabin
R A
RA
D000631:Aminopyridines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015283:Citalopram / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000631:Aminopyridines; D015283:Citalopram; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D010622:Phencyclidine; D010879:Piperazines; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; C081293:WAY 100135; C015068:1-(3-chlorophenyl)piperazine