Response suppression induced with selective 5-HT agonists can be differentially blocked with LY53857 in an animal model of depression.
Studies from this laboratory have demonstrated that administration of the selective 5-HT2/1C antagonist LY53857 can block 5-HTP-induced response suppression. To further investigate the serotonergic mechanisms involved in this effect, we decided to test the capacity of LY53857 to block response suppression induced with two selective 5-HT agonists. After a 15 minute baseline period, rats trained to press a lever for milk reinforcement on a VI 1' schedule were given IP injections of 1.0 mg/kg DOI, or 1.0 mg/kg 8-OH-DPAT to induce response suppression. Subsequently, rats were injected with 1.0 mg/kg LY53857 1 hour prior to DOI- or 8-OH-DPAT-induced response suppression. Preinjections with LY53857 resulted in a 100% blockade of DOI-induced response suppression whereas the same dose did not block response suppression induced with 8-OH-DPAT. These results indicate that the 5-HTP-induced response suppression shows some pharmacological similarity to DOI-induced response suppression and may be mediated through 5-HT2 and/or 5-HT1C receptors.
Engleman
E A
EA
Department of Psychiatry, Indiana University School of Medicine, Indianapolis.
Murphy
J M
JM
Zhou
F C
FC
Hingtgen
J N
JN
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000503:physiopathology*; D004195:Disease Models, Animal; D004873:Ergolines / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012054:Reinforcement, Psychology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D000662:Amphetamines; D004873:Ergolines; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C076823:1-(2,5-dimethyl-4-iodophenyl)-2-aminopropane; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C032663:LY 53857