Intracerebroventricular administration of the β3-adrenoceptor agonist CL 316243 causes Fos immunoreactivity in discrete regions of rat hypothalamus

Intracerebroventricular (i.c.v.) administration of the β₃-AR agonist BRL37344 causes dose dependent decreases in food intake in rats suggesting a role for β₃-AR in the central control of feeding. We have conducted experiments investigating the effects of i.c.v. administration of the selective β₃-AR agonist CL316243 on Fos expression to determine whether β₃-AR stimulation affects neurones within specific brain nuclei. Significantly higher numbers of Fos positive cells were found in the rats treated i.c.v. with CL316243 compared with control rats in the paraventricular hypothalamus, lateral hypothalamic area, ventromedial hypothalamic nucleus and dorsal hypothalamic area. Pre-treatment with the selective β₃-AR antagonist SR59230A resulted in a significant decrease in the number of Fos positive cells in all those areas compared with rats treated with CL316243 alone. These experiments demonstrate that i.c.v. administration of selective β₃-AR agonist causes neuronal activation in hypothalamic areas important in the central regulation of appetite via a β₃-AR mediated effect.