The alpha7 nicotinic receptor agonist SSR180711 increases activity regulated cytoskeleton protein (Arc) gene expression in the prefrontal cortex of the rat

TY - JOUR

T1 - The alpha7 nicotinic receptor agonist SSR180711 increases activity regulated cytoskeleton protein (Arc) gene expression in the prefrontal cortex of the rat

AU - Kristensen, Søren

AU - Thomsen, Morten Skøtt

AU - Hansen, Henrik H

AU - Timmermann, Daniel B

AU - Hay-Schmidt, Anders

AU - Mikkelsen, Jens D

PY - 2007/5/17

Y1 - 2007/5/17

N2 - Nicotinic alpha7 acetylcholine receptors (alpha7 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 alpha7 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 alpha7 nAChR agonist, SSR180711 (1, 3 and 10 mg/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 alpha7 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.

AB - Nicotinic alpha7 acetylcholine receptors (alpha7 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 alpha7 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 alpha7 nAChR agonist, SSR180711 (1, 3 and 10 mg/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 alpha7 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.

KW - Acetylcholine

KW - Animals

KW - Attention

KW - Attention Deficit Disorder with Hyperactivity

KW - Bicyclo Compounds, Heterocyclic

KW - Cytoskeletal Proteins

KW - Dose-Response Relationship, Drug

KW - Gene Expression Regulation

KW - In Situ Hybridization

KW - Male

KW - Memory

KW - Memory Disorders

KW - Nerve Tissue Proteins

KW - Nicotinic Agonists

KW - Prefrontal Cortex

KW - RNA, Messenger

KW - Rats

KW - Rats, Wistar

KW - Receptors, Nicotinic

KW - Synaptic Transmission

KW - Time Factors

KW - Up-Regulation

KW - alpha7 Nicotinic Acetylcholine Receptor

U2 - 10.1016/j.neulet.2007.03.016

DO - 10.1016/j.neulet.2007.03.016

M3 - Journal article

C2 - 17379406

SN - 0167-6253

VL - 418

SP - 154

EP - 158

JO - Neuroscience letters. Supplement

JF - Neuroscience letters. Supplement

IS - 2

ER -