TY - JOUR T1 - Role of the fourth cerebroventricle in mediating rat plasma ACTH responses to intravenous nicotine. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 623 LP - 630 VL - 252 IS - 2 AU - S G Matta AU - K M McAllen AU - B M Sharp Y1 - 1990/02/01 UR - http://jpet.aspetjournals.org/content/252/2/623.abstract N2 - Peripherally administered nicotine elevates rat plasma adrenocorticotropic hormone (ACTH) levels, acting at brain regions adjacent to or downstream from the third cerebroventricle. Studies evaluated whether the paraventricular nucleus (PVN) mediates directly the ACTH response to nicotine administered i.v. and if regions adjacent to the fourth ventricle (IV) are involved. Direct involvement of the PVN in the release of ACTH in response to i.v. nicotine (0.03 or 0.01 mg/kg b.wt.) was refuted by studies in which the administration of the nicotinic cholinergic antagonist, mecamylamine (20 or 40 micrograms bilaterally adjacent to the PVN), failed to block ACTH secretion. To activate sites distal to the third ventricle, nicotine (0.25, 0.5, 2.5 or 5.0 micrograms) was injected into the IV; ACTH levels peaked between 3 and 7 min. Nicotine 0.25 micrograms injected into the IV elevated ACTH to levels within the range of those produced by i.v. nicotine (0.03 mg/kg b.wt.). To confirm that sites accessible from the IV are involved, mecamylamine was administered i.v. (0.5 or 1.0 mg/kg b.wt.) or into the IV (4 or 40 micrograms) and nicotine was delivered by the opposite route. Intravenous mecamylamine reduced the plasma ACTH response to 0.25 micrograms of nicotine in the IV. Mecamylamine, administered into the IV before i.v. nicotine (0.03 mg/kg b.wt.) antagonized the effect of nicotine. These results indicate that stimulation of ACTH secretion by nicotine delivered i.v. occurs via structures accessible from the IV. In contrast to prevailing ideas, the PVN does not appear to be the direct site of action of nicotine. ER -