The α7 nicotinic receptor agonist SSR180711 increases activity regulated cytoskeleton protein (Arc) gene expression in the prefrontal cortex of the rat

Abstract: Nicotinic α7 acetylcholine receptors (α7 nAChR) have been shown to enhance attentional function and aspects of memory function in experimental models and in man. The protein Arc encoded by the effector immediate early gene arc or arg3.1 has been shown to be strongly implicated in long-term memory function. We have sought to determine if α7 nAChR mediate the stimulation of arc gene expression, and if so, where in the brain such activation may occur using semi-quantitative in situ hybridisation. Administration of the novel and selective α7 nAChR agonist, SSR180711 (1, 3 and 10mg/kg) to adolescent rats, produced a dose- and time-dependent increase in the expression of Arc mRNA in the prefrontal cortex and the ventral orbital cortex. By contrast, no change in mRNA levels was detected in the parietal cortex and the CA1 of the hippocampus. These data show that α7 nAChR activates a subset of neurons in the rat prefrontal cortex and this activation likely is important for the attentional effects of this new class of drugs. [Copyright &y& Elsevier]