Dopamine and reward: The anhedonia hypothesis 30 years on

Abstract

The anhedonia hypothesis – that brain dopamine plays a critical role in the subjective pleasure associated with positive rewards – was intended to draw the attention of psychiatrists to the growing evidence that dopamine plays a critical role in the objective reinforcement and incentive motivation associated with food and water, brain stimulation reward, and psychomotor stimulant and opiate reward. The hypothesis called to attention the apparent paradox that neuroleptics, drugs used to treat a condition involving anhedonia (schizophrenia), attenuated in laboratory animals the positive reinforcement that we normally associate with pleasure. The hypothesis held only brief interest for psychiatrists, who pointed out that the animal studies reflected acute actions of neuroleptics whereas the treatment of schizophrenia appears to result from neuroadaptations to chronic neuroleptic administration, and that it is the positive symptoms of schizophrenia that neuroleptics alleviate, rather than the negative symptoms that include anhedonia. Perhaps for these reasons, the hypothesis has had minimal impact in the psychiatric literature. Despite its limited heuristic value for the understanding of schizophrenia, however, the anhedonia hypothesis has had major impact on biological theories of reinforcement, motivation, and addiction. Brain dopamine plays a very important role in reinforcement of response habits, conditioned preferences, and synaptic plasticity in cellular models of learning and memory. The notion that dopamine plays a dominant role in reinforcement is fundamental to the psychomotor stimulant theory of addiction, to most neuroadaptation theories of addiction, and to current theories of conditioned reinforcement and reward prediction. Properly understood, it is also fundamental to recent theories of incentive motivation.

Pain-Related Depression of the Mesolimbic Dopamine System in Rats: Expression, Blockade by Analgesics, and Role of Endogenous κ-opioids

“…ICSS is mediated in part by activation of mesocorticolimbic dopamine (DA) neurons that originate in the ventral tegmental area and project to terminal regions that include nucleus accumbens (NAc) (Stellar and Stellar, 1985;Wise, 2008). The mesocorticolimbic DA system has a well-established role in mediating the rewarding effects of not only brain stimulation, but also natural reinforcers (eg, preferred foods) and of abused drugs (eg, stimulants and opioids) (Di Chiara and Imperato, 1988a;Wise, 2008).…”

“…The mesocorticolimbic DA system has a well-established role in mediating the rewarding effects of not only brain stimulation, but also natural reinforcers (eg, preferred foods) and of abused drugs (eg, stimulants and opioids) (Di Chiara and Imperato, 1988a;Wise, 2008). Depression of ICSS by noxious stimuli suggests that noxious stimuli may also depress signaling by mesolimbic DA neurons.…”

HIT and brain reward function: A case of mistaken identity (theory)

“…Secondly, in pursuing it, advocates of HIT incur the burden of providing a general answer about the conditions on research maturation. More problematically still, the maneuver may backfire, since cases where identity claims are made only after research has sufficiently 5 For an overview of this literature, see Hornykiewicz (1986Hornykiewicz ( , 2002Milner (1991); Marsden (2006);Wise (2008). 6 In more recent literature in the 1990s and beyond, the computational functions of DA in relation to reward prediction error, incentive salience, and precision have become important research foci (see Colombo, 2014 for an overview; see also Colombo & Wright, 2017 developed may be cases that better support the traditional identity theory over HIT.…”

What’s Special about the Ethical Challenges of Studying Disorders with Altered Brain Activity?

“…Thus, there is a particular issue with respect to shifts in the baseline behavioural response in studies, which directly or indirectly manipulate dopaminergic neuronal activity in a manner likely to result in changes in hedonic tone (Wise 2008). When tasks are adapted to run with different reinforcers, direct comparability between task variants is compromised and there may be a substantial body of work completed with the reinforcer originally adopted.…”