Reward without Dopamine

Abstract

Dopamine (DA) is believed to play a fundamental role in reward processes. Virtually all drugs of abuse activate dopaminergic systems, as do "natural" rewards such as sexual interaction and food. Sweet-tasting solutions, for example, are a well characterized natural reward. In the present experiments, we used mice that cannot make DA (DD mice) to test the hypothesis that DA is necessary for reward. Sucrose preference, assessed with a computerized "lickometer," was used to determine whether DD mice respond preferentially for rewarding stimuli. DD mice preferentially chose sucrose over water, and also preferred the noncaloric sweetener saccharin. Furthermore, the rate of licking, bout size, and length were greater in DD mice drinking sweets than in controls. These data refute the necessity of DA for the reward processes manifested by sucrose preference. However, DD mice initiated licking less frequently than control mice and had fewer total licks. We suggest that DD mice have a deficit of goal-directed behavior that is not specific to reward processes. Lastly, juvenile DD mice demonstrate robust sucrose preference before experience with food in the presence of DA. Thus, DA is not required for mice to learn to consume sweet solutions preferentially. We conclude that DA is not required to find the sweet tastes of sucrose or saccharin rewarding.

The Hypothalamic Neuropeptide Melanin-Concentrating Hormone Acts in the Nucleus Accumbens to Modulate Feeding Behavior and Forced-Swim Performance

“…Although genetic elimination of dopamine results in severely hypophagic mice (Zhou and Palmiter, 1995;Szczypka et al, 2001), it is difficult to distinguish between the role of dopamine in locomotor activity and movement control versus feeding. In fact, pharmacological and genetic experiments in the AcSh have suggested that dopamine is not absolutely necessary for feeding but may have a primary role in modifying the incentive drive for food (Nowend et al, 2001;Baldo et al, 2002;Cannon and Palmiter, 2003). It also is possible that MCH, through its action in the AcSh, is a starvation-induced hypothalamic signal that modulates the AcSh reward pathway to increase the drive to feed (Kelley and Berridge, 2002;Saper et al, 2002).…”

Affective neuroscience of pleasure: reward in humans and animals

“…One line of evidence against a pleasure-causing role is that mesolimbic dopamine neurons may not reliably be activated by pleasure per se but instead by predictive, motivational, or attentional properties rather than hedonic properties of reward stimuli (Carelli 2004;Cheer et al 2007;Redgrave and Gurney 2006;Salamone et al 2007;Schultz et al 1997). Another line of evidence is that, when 'liking' versus 'wanting' are teased apart by brain manipulations, specific manipulation of dopamine signaling either up or down simply fail to shift 'liking' reactions to pleasure reliably in either animals or humans (Berridge 2007;Brauer and De Wit 1997;Cannon and Palmiter 2003;Evans et al 2006;Leyton 2008;Leyton et al 2002;Leyton et al 2005;Peciña et al 2003;Robinson et al 2005;Tindell et al 2005;Volkow et al 2002;Volkow et al 2006). A third line of evidence is that dopamine systems may also be activated by aversive or frankly non-rewarding stimuli, at least tonic dopamine release pulses that last on the order of a few minutes (Ferrari et al 2003;Horvitz 2000;Salamone 1994;Scott et al 2006).…”

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

“…For instance, transgenic mice incapable of producing dopamine still exhibit preference for sweetened sucrose solution over water (Cannon and Palmiter, 2003) and develop conditioned place preference (CPP) for a morphine-paired chamber (Hnasko et al, 2005). There are some caveats to the validity of this transgenic method (eg, the mice must be treated daily with L-DOPA to survive and given caffeine to overcome hypoactivity), but these experiments and others indicate that non-dopaminergic molecular mechanisms may also mediate reinforcement learning.…”