EXPRESSION OF FOS PROTEIN IN RAT-BRAIN FOLLOWING ADMINISTRATION OF A NICOTINIC ACETYLCHOLINE-RECEPTOR AGONIST EPIBATIDINE

Epibatidine (6-chloro-3-pyridyl)-7-azabicyclo-[2.2.1]heptane), an extr act of frog skin, is a novel and highly potent agonist for the nicotin ic acetylcholine (ACh) receptor. The present study was undertaken to e xamine the expression of Fos protein in several rat brain regions foll owing an acute administration of epibatidine. Furthermore, we also stu died the role of the dopamine D-1 and D-2 receptors and the N-methyl-D -aspartate (NMDA) receptor, and nicotinic ACh receptor in the expressi on of Fos protein by epibatidine. A single administration of epibatidi ne (5, 10, 50 mu g/kg) caused a marked induction of Fos-immunoreactivi ty in the prefrontal cortex, medial striatum, nucleus accumbens, amygd ala and superior colliculus of rat brain. In these regions, pretreatme nt with SCH 23390 (1.0 mg/kg), a dopamine D-1 receptor antagonist, MK- 801 (1.0 mg/kg), a NMDA receptor antagonist, and mecamylamine (5.0 mg/ kg), a nicotinic Ach receptor antagonist, inhibited the induction of F os protein by epibatidine (10 mu g/kg). Pretreatment with sulpiride, a dopamine D-2 receptor antagonist, blocked the induction of Fos protei n in the prefrontal cortex and 1:he core region of accumbens nucleus, but not in the medial striatum and the shell division of nucleus accum bens of rat brain. These results suggest that epibatidine induced the expression of Fos protein in several regions of rat brain, and that do pamine D-1 receptor, NMDA receptor, and nicotinic ACh receptor may pla y a role in the expression of Fos protein by epibatidine in rat brain. Furthermore, dopamine D-2 receptor may, in part, play a role in epiba tidine induced expression of Fos protein in the prefrontal cortex and the core region of nucleus accumbens, but not in the medial striatum a nd the shell division of nucleus accumbens of rat brain. (C) 1998 Else vier Science B.V. All rights reserved.