Serotonin microinjected into the nucleus raphe obscurus increases intragastric pressure in the rat via a vagally mediated pathway
Krowicki, Z.K.; Hornby, P.J.
Journal of Pharmacology and Experimental Therapeutics 265(1): 468-476
1993
ISSN/ISBN: 0022-3565 PMID: 8097247 Document Number: 420970
The purpose of the present study was to investigate the effect of microinjection of serotonin (5-HT) and selected 5-HT receptor subtype agonists and antagonists into the caudal nucleus raphe obscurus on gastrointestinal motor activity in urethane-chloralose anesthetized rats. Serotonin (0.6-18.0 nmol) dose-dependently increased intragastric pressure, and this effect was abolished by peripherally administered atropine (0.5-1.0 mg/kg, i.v.). Microinjection of a 5-HT-1A receptor agonist, 8-hydroxy-N,N-dipropyl-2-amino-tetralin hydrobromide (0.06-12.0 nmol), a 5-HT-1C/2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (4.5 and 18.0 nmol), as well as a 5-HT-3 receptor agonist, 1-(m-chlorophenyl)-biguanide hydrochloride (0.6-18.0 nmol), also resulted in increases in intragastric pressure. The gastric excitatory effect of 5-HT (6.0 nmol) was markedly reduced by prior microinjection of a 5-HT-1/2 receptor antagonist, methiothepin (200 nmol), into the same site, as well as by i.v. administration of a 5-HT-2/1C antagonist, ketanserin (2.5 mg/kg). The effect of 5-HT (6.0 nmol) on intragastric pressure was completely blocked by i.v. administration of a mixture of the 5-HT-1A receptor antagonist 1-(2-methoxyphenyl)-4-(-(2-phthalimido)butyl)piperazinehydrobromide (3.5 mg/kg), ketanserin (2.5 mg/kg) and the 5-HT-3 receptor antagonist 3-tropanyl-3,5-dichlorobenzoate (2.5 mg/kg). These results indicate that 5-HT activates gastric motor function in the caudal nucleus raphe obscurus via a vagally mediated pathway and that the activation of multiple 5-HT receptor subtypes is required for the gastric excitatory effect of 5-HT.