Effect of repeated co-treatment with fluoxetine and amantadine on the behavioral reactivity of the central dopamine and serotonin system in rats.
In the present study we found that repeated co-treatment with fluoxetine and amantadine for 14 days (but not for 7 days) enhanced the hyperactivity induced by amphetamine or quinpirole (a dopamine D(2/3) agonist), compared to treatment with either drug alone. Whereas repeated co-treatment with fluoxetine and amantadine for 7 days more potently inhibited the behavioral syndrome evoked by the 5-hydroxytryptamine (5-HT)(1A) receptor agonist (+/-)-8-hydroxy-2(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT), it did not change the action of the 5-HT(2) receptor agonist (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (/+/-/-DOI). The obtained results support the hypothesis that repeated co-treatment with fluoxetine and amantadine may evoke more effective antidepressant activity than treatment with fluoxetine alone. Moreover, our results suggest that 5-HT(1A) receptors are useful targets for the development of more rapidly acting and more effective medication.
Rogóz
Zofia
Z
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. rogoz@if-pan.krakow.pl
Skuza
Grazyna
G
D000547:Amantadine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D000547:Amantadine; D003913:Dextroamphetamine; D015259:Dopamine Agents; D005473:Fluoxetine; D019257:Quinpirole; D044282:Receptor, Serotonin, 5-HT1A; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D044348:Receptors, Serotonin, 5-HT2; D017367:Selective Serotonin Reuptake Inhibitors