Effect of chronic treatment on the cardiovascular and behavioral responses of 8-OH-DPAT in conscious normotensive rats.
Cardiovascular and behavioral responses induced by intravenous administration of the serotonin (5-HT)1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were studied in conscious normotensive rats either after a single administration, after repeated subcutaneous treatments (1 mg/kg daily for 3 days), or after chronic intravenous infusion (200 micrograms/kg per h for 72 h). In naive rats, a single intravenous treatment with 10, 30 or 100 micrograms/kg 8-OH-DPAT produced a blood pressure reduction of approximately 10% and a heart rate reduction of 15-20%. The duration of blood pressure and heart rate reduction was dose-dependent. Behavioral responses were observed (i.e. reciprocal forepaw treading, flat body posture, hind limb abduction and headweaving), the severity and duration of which were also dose-dependent. Subcutaneous pretreatment with 8-OH-DPAT greatly reduced the behavior responses but did not alter the hypotensive or the heart rate response to a single intravenous administration of 8-OH-DPAT. Blood pressure and behavior were not monitored during the subcutaneous pretreatment period. Intravenous infusion of 8-OH-DPAT attenuated both the cardiovascular and behavioral effects to post-infusion intravenous treatment. The differential tolerance development to these responses suggests that 8-OH-DPAT may exert its blood pressure response and its behavior response through two distinct mechanisms.
Kolbasa
K P
KP
Cardiovascular Diseases Research, Upjohn Laboratories, Kalamazoo, MI 49001.
McCall
R B
RB
Ludens
J H
JH
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003243:Consciousness; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*
D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin