Anhedonia hypothesis

Koob, George F. 1982. "The Dopamine Anhedonia Hypothesis AI Pharmacological Phrenology." Behavioral and Brain Sciences 5 63-64. 

Soon after the formalization of the original anhedonia hypothesis, however, Phillips and Fibiger (1979) reported that neuroleptics reduce responding also when given under extinction moreover, Gray and Wise (1980) observed that DA receptor blockers impaired... 

As a result of these early studies, therefore, four main hypotheses were considered to explain the effect of DA-receptor blockers on instrumental behavior (1) Blunting of the rewarding properties of primary reinforcers (original anhedonia hypothesis) ... 

Loss of the incentive-motivational and arousal properties of primary reinforcers (rewards) and of stimuli conditioned to them (incentives) (revised anhedonia hypothesis) ... 

The original anhedonia hypothesis has been tested in studies of the effects of DA receptor antagonists and 6-OHDA lesions of DA neurons on operant and free-feeding measures of sucrose or saccharin reward. However, in spite of the large number of studies performed (reviewed by Di Chiara, 2000) the results obtained are compatible with any of the possibilities indicated above and therefore do not allow to be distinguished. 

DA has been implicated in the expression as well as in the acquisition of incentive-motivation. Various hypotheses, since the revised anhedonia hypothesis, assume that DA mediates or modulates the expression of the incentive properties of stimuli. However, apart from their common incentive label, these hypotheses differ substantially in some aspects critical for their testing and for their working character. Thus, the term incentive has been utilized in two different senses a specific sense , referring to the directional response-eliciting properties of stimuli and in a nonspecific sense , referring to their generic response-arousing properties. We indicate the first as stimulus-bound incentive and the second as incentive arousal. 

The notion of an incentive arousal role of DA has some similarities with that envisioned by Wise (1982) in his revised anhedonia hypothesis. It is notable, however, that, even in the revised anhedonia hypothesis, the main function of DA remains that of mediating hedonia, consistently with the notion that incentives acquire not only the response-eliciting but also the hedonic properties of the rewards to which they are conditioned, thus becoming conditioned rewards (Bindra, 1974, 1978). 

Salamone JD, Cousins MS, Snyder BJ (1997) Behavioral functions of nucleus accumbens dopamine empirical and conceptual problems with the anhedonia hypothesis. Neurosci Biobehav Rev 27 341-359. 

Wise RA (1982) Neuroleptics and operant behavior the anhedonia hypothesis. Behav Brain Sci 5 39-87. 

After long-term administration, antidepressants may enhance dopaminergic neurotransmission, even if direct acute effects are absent (Serra et al. 1990b). For example, the stress-induced decrease in the binding of quinpirole, an agonist of Dj and Dj receptors, can be reversed by chronic imipramine treatment [Papp et al. 1994). These and related data, however, do not allow the formulation of a dopamine hypothesis of depression, but rather point to a role for decreased dopaminergic neurotransmission in specific neuronal circuits that are responsible for those depressive syndromes associated with motivational loss, psychomotor retardation, and anhedonia [Willner 1995). 

An advantage of the hedonic allostasis hypothesis is that it provides a basis for the strong comorbidity of drug addiction and depression. However, this relationship with depression is also the limit of the hypothesis. Thus, anhedonia induced by cocaine withdrawal has been proposed as a model of depression also on the basis of the observation that antidepressants reverse withdrawal-induced anhedonia yet, antidepressants do not provide a treatment for drug addiction. Therefore it would appear that anhedonia is a condition associated to drug addiction but is not the factor that sustains its maintenance or its resumption after a long period of abstinence. 

Schizophrenia is a chronic disease characterized by, e.g. delusions, hallucinations, affective blunting, anhedonia, social withdrawal, disorganized speech, attention deficits and cognitive deficits. An extensive number of articles have been published about the dopamine hypothesis of schizophrenia (see, e.g. Sedvall and Farde, 1995 Carlsson et al., 1997 Joyce and Meador-Woodruff, 1997 Weinberger, 1997 Willner, 1997 Bennett, 1998 Laruelle, 1998 Baumeister and Francis, 2002), so below we provide only a brief review of the dopaminergic alterations that have been detected postmortem in association with this disorder. 

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