Treatment with a muscarinic acetylcholine receptor antagonist impairs the acquisition of conditioned reward learning in rats

CaMKII antagonism in the ventral tegmental area impairs acquisition of conditioned approach learning in rats

“…We have also shown that the number of VTA DA neurons activated is significantly correlated with the capacity of a CS to elicit conditioned approach responses . Further, we have shown that the antagonism of mACh receptors in the VTA (Sharf and Ranaldi 2006;Sharf et al 2006) or systemically (Nisanov et al 2016) impairs the acquisition of reward-related learning. Likewise, antagonism of NMDA receptors in the VTA impairs the acquisition of reward-related learning (Kest et al, 2012;Ranaldi et al, 2011;Zellner, Kest, & Ranaldi, 2009).…”

“…We have proposed a model stipulating that concurrent activation of the CS-and US-relevant receptors on DA neurons in the VTA is necessary for CSs to gain the capacity to activate these DA neurons (Zellner & Ranaldi, 2010). We propose that the US input is comprised of acetylcholine (ACh) stimulation of muscarinic receptors (mACh) on DA neurons (Sharf and Ranaldi 2006;Sharf et al 2006;Zellner et al 2009;Ranaldi et al 2011;Kest et al 2012;Nisanov et al 2016;Galaj et al 2017). The major sources of ACh to the VTA are the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDTg) hindbrain nuclei (Garzón, Vaughan, Uhl, Kuhar, & Pickel, 1999;Holmstrand & Sesack, 2011;Oakman, Faris, Kerr, Cozzari, & Hartman, 1995;Omelchenko & Sesack, 2006).…”