title: The effects of Cirazoline, an alpha-1 adrenoreceptor agonist, on the firing rates of thermally classified anterior hypothalamic neurons in rat brain slices.
abstract: Peripheral exposure to LPS induces a biphasic fever thought to be initiated via vagal afferents to the preoptic area of the anterior hypothalamus (POAH), an important thermoregulatory control center in the brain. Previous studies have shown that norepinephrine synaptically mediates this Prostaglandin E(2) (PGE(2))-dependent change in temperature through the selective activation of alpha-2 adrenoreceptors (AR). However, there is clear evidence that alpha-1 AR activation of thermoregulatory hypothalamic neurons will result in a rapid hyperthermia that is not dependent on PGE(2). This direct action of norepinephrine in the POAH was tested in the present study by recording the single-unit activity of POAH neurons in a tissue slice preparation from the adult male rat, in response to temperature and the selective alpha-1 AR agonist Cirazoline (1-100 microM). Neurons were classified as either warm sensitive or temperature insensitive. Warm sensitive neurons responded to Cirazoline with a decrease in firing rate, while temperature insensitive neurons showed a firing rate increase. These responses are similar to those reported for PGE(2) and suggest that both warm sensitive and temperature insensitive neurons in the POAH are important in mediating this alpha-1 AR-dependent hyperthermic shift in body temperature.
authors.affiliation: Department of Biology and Program in Neuroscience, Millington Hall, Room 116, College of William and Mary, Williamsburg, VA 23187, USA.
authors.forename: Ted E
authors.initials: TE
authors.lastname: Imbery
authors.forename: Mitra S
authors.initials: MS
authors.lastname: Irdmusa
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Speidell
authors.forename: Mark S
authors.initials: MS
authors.lastname: Streer
authors.forename: John D
authors.initials: JD
authors.lastname: Griffin
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000166:cytology*; D006358:Hot Temperature; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; C014282:cirazoline