Effect of chronic treatment on the cardiovascular and behavioral responses of 8-OH-DPAT in conscious normotensive rats

• Published in: European journal of pharmacology Vol. 193; no. 3; p. 275
• Main Authors: Kolbasa, K P, McCall, R B, Ludens, J H
• Format: Journal Article
• Language: English
• Published: Netherlands 14-02-1991
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Behavior, Animal - drug effects; Blood Pressure - drug effects; Cardiovascular System - drug effects; Consciousness; Drug Administration Schedule; Drug Tolerance; Female; Heart Rate - drug effects; Infusions, Intravenous; Injections, Intravenous; Injections, Subcutaneous; Rats; Rats, Inbred Strains; Serotonin Antagonists - administration & dosage; Serotonin Antagonists - pharmacology; Tetrahydronaphthalenes - administration & dosage; Tetrahydronaphthalenes - pharmacology
• ISSN: 0014-2999
• DOI: 10.1016/0014-2999(91)90140-L

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.