The α4β2 nicotinic acetylcholine receptor agonist TC-2559 impairs long-term potentiation in the dentate gyrus in vivo

Nicotinic acetylcholine receptors (nAChR) are widely expressed throughout the nervous system, are involved in some fast excitatory neurotransmission, and play an important role in modulating the release of several neurotransmitters, including the major excitatory and inhibitory neurotransmitters, glutamate and GABA. We used a recently characterised alpha 4 beta 2 nAChR subunit selective partial agonist, TC-2559, to study the effect of alpha 4 beta 2 nAChR activation on synaptic plasticity in the medio-dorsal perforant pathway input to the dentate gyrus, in the intact nervous system in vivo. We show for the first time, that the selective activation of alpha 4 beta 2 containing nAChR can reduce the level of long-term potentiation (LTP) induced by high frequency stimulation, an effect that was reversed by the selective antagonist, dihydro-p-erythroidine (D beta HE). This modulator role of nAChRs is in contrast to previous findings that used broad spectrum agonists, highlighting the complex actions of nicotine. (c) 2006 Elsevier Ireland Ltd. All rights reserved.