Effect of the 5HT1A receptor partial agonist buspirone on colorectal distension-induced pseudoaffective and behavioral responses in the female Wistar rat.
In the present study, we have evaluated the visceral analgesic property of buspirone, a 5HT(1A) receptor partial agonist, on colorectal distension-induced mean arterial pressure and behavioral changes in anesthetized and awake Wistar rats, respectively. The selection of the rat strain was based on the observation that anesthetized Wistar rats exhibited a more prominent mean arterial pressure change in response to colorectal distention when compared to other strains (Sprague-Dawley, Wistar-Kyoto and Spontaneously Hypertensive). Buspirone dose-dependently (0.1-1 mg/kg, i.v.) antagonized mean arterial pressure change over a range of distensions (10-90 mmHg). In parallel studies conducted in awake animals, buspirone (1-5 mg/kg, s.c.) attenuated the abdominal withdrawal response, a nociceptive behavior, in response to colorectal distension. This effect was antagonized by co-administration of the 5-HT(1A) receptor antagonist N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2- pyridinylcyclohexanecarboxamide (WAY-100635) (5 mg/kg, s.c.). We conclude that buspirone exhibits significant visceral analgesic property in two models of abdominal nociception.
Sivarao
Digavalli V
DV
Neuroscience Drug Discovery (3CD-422), Pharmaceutical Research Institute, Bristol Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06067, USA. siva.digavalli@bms.com
Newberry
Kimberly
K
Lodge
Nicholas J
NJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002065:Buspirone / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D005260:Female; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012007:Rectum / Q000187:drug effects* / Q000502:physiology; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013045:Species Specificity
D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D002065:Buspirone