Blockade of muscarinic acetylcholine receptors in the ventral tegmental area blocks the acquisition of reward-related learning

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

“…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).…”

Aberrations in Incentive Learning and Responding to Heroin in Male Rats After Adolescent or Adult Chronic Binge‐Like Alcohol Exposure

“…Here, stimuli (conditioned stimuli, CSs) that are associated with primary rewards (unconditioned stimuli, USs) acquire the ability to produce effects similar to the US including the capacity to elicit conditioned approach responses and to function as conditioned rewards in their own right (Beninger and Ranaldi, 1992; Skinner, 1938). We have proposed and demonstrated through a series of studies that the acquisition by a CS of the capacity to function as such depends on its acquired capacity to activate the same neural system—ventral tegmental area (VTA) dopamine (DA) neurons—that are unconditionally activated by the primary reward (Galaj et al, 2017; Galaj and Ranaldi, 2018; Kest et al, 2012; Ranaldi, 2014; Ranaldi et al, 2011; Zellner et al, 2009; Zellner and Ranaldi, 2010). Pedunculopontine tegmental, basolateral amygdala, and prefrontal cortical afferents to the VTA DA system, a system that plays a critical role in conditioned reward learning (Burns et al, 1993; Everitt and Robbins, 1992; Pears et al, 2003; Ranaldi, 2014), are severely impacted by CIE exposure (Arendt et al, 1988; Broadwater et al, 2018; Coleman et al, 2014; Jury et al, 2017; McGinnis et al, 2019; Morales et al, 2018; Pereira et al, 2019; Schindler et al, 2016; Vetreno et al, 2014).…”