Dual Role of Medial A10 Dopamine Neurons in Affective Encoding

Abstract

Increasing evidence suggests that the activation of medial A10 neurons mediates positive affective encoding. However, little is known about the functions of the inhibition of midbrain dopamine neurons. Here we show evidence suggesting that the inhibition of medial A10 neurons mediates a negative affective state, leading to negative affective encoding, whereas blunting the activation of medial A10 neurons disrupts positive affective encoding involving food reward. We used a microinjection procedure, in which the D 2 dopamine receptor agonist quinpirole was administered into the cell body region of the dopamine neurons, a procedure that reduces dopamine cell firing. Microinjections of quinpirole into the posteromedial ventral tegmental area, but not its more lateral counterparts, led to conditioned place aversion. Quinpirole administration to this site also decreased food intake and basal dopamine concentration in the ventromedial striatum, a major projection area of medial A10 neurons. In addition, moderate quinpirole doses that did not lead to conditioned place aversion or disrupt food intake abolished food-conditioned place preference, suggesting that blunting dopamine impulse activity in response to food reward disrupts positive affective encoding in associated external stimuli. Our data support the hypothesis that activation of medial A10 dopamine neurons mediates a positive affective state, leading to positive affective encoding, while their inhibition mediates a negative affective state, leading to negative affective encoding. Together with previous findings, we propose that medial A10 neurons are an important component of the mechanism via which animals learn to avoid negative incentive stimuli.

Increased Dopamine Receptor Activity in the Nucleus Accumbens Shell Ameliorates Anxiety during Drug Withdrawal

“…Furthermore, reduced dopaminergic signaling in the NAc is associated with emotional signs of nicotine withdrawal (Cryan et al, 2003;Paterson et al, 2007). Further confirmation that the mesolimbic dopaminergic system contributes to withdrawal from other addictive drugs would cohere with a growing body of literature demonstrating that it is also involved in a wide variety of aversive behaviors, including conditioned place aversion (Acquas et al, 1989;Calcagnetti and Schechter, 1991;Schechter and Meechan, 1994;Liu et al, 2008), fear conditioning (Borowski and Kokkinidis, 1996;Nader and LeDoux, 1999;Pezze and Feldon, 2004;Fadok et al, 2009;Muschamp et al, 2011), anxiety (Fride and Weinstock, 1988;Barrot et al, 2002;Barrot et al, 2005;Meloni et al, 2006;Rezayof et al, 2009;Richard and Berridge, 2011;Zweifel et al, 2011), intrinsic aversion to gustatory cues (Roitman et al, 2008), conditioned taste aversion Fenu et al, 2001), responses to stress (Geyer and Segal, 1974;Herman et al, 1982;Inglis and Moghaddam, 1999;Belda and Armario, 2009), and responses to nociceptive stimulation (Gear et al, 1999;Becerra et al, 2001;Barrot et al, 2002).…”

“…Decreased dopaminergic activity has been shown to contribute to the production of negative emotional states (Stinus et al, 1990;Liu et al, 2008;Nestler and Carlezon, 2006) and manipulation of dopaminergic signaling attenuates conditioned place aversion (Bechara et al, 1995;Laviolette et al, 2002;Chartoff et al, 2006;but see Caillé et al, 2003) and other signs of opiate withdrawal (Harris and Aston-Jones, 1994;Rodríguez-Arias et al, 1999). Importantly, the initial increase in NAc dopamine release following acute exposure to 10 mg/kg of morphine would have largely dissipated at the time at which spontaneous withdrawal-potentiated startle is observed (Di Chiara and Imperato, 1988;Rothwell et al, 2009).…”

Neurotensin inhibits both dopamine- and GABA-mediated inhibition of ventral tegmental area dopamine neurons

“…D2Rs in VTA DA neurons regulate DA neuron activity and also regulate DA-mediated behaviors. For example, injection of quinpirole, a D2R agonist, directly into the VTA causes conditioned place aversion, blocks food-induced conditioned place preference, decreases food intake, and decreases cocaineinduced reinstatement (Liu et al 2008;Xue et al 2011). Furthermore selective knockout of autoreceptor D2Rs within midbrain DA neurons causes increased motor activity to a novel environment, increased food self-administration, and increased responses to cocaine such as increased locomotor activity and conditioned place preference compared with wildtype mice (Anzalone et al 2012;Bello et al 2011).…”

Migraine and Reward System—Or Is It Aversive?

“…This test provides an understanding of the contribution of processes underlying motivation and reward [34], and is frequently used to assess affective states by measuring the time spent in an environment previously associated with motivationally salient stimuli (e.g., drugs or food). Pavlovian conditioning is involved in the acquisition of a place preference for a drug (most commonly studied are illicit drugs).…”