Investigating dopamine and glucocorticoid systems as underlying mechanisms of anhedonia (2018)

Psychopharmacology (Berl). 2018 Aug 22. doi: 10.1007/s00213-018-5007-4.

Lamontagne SJ1, Melendez SI1, Olmstead MC2,3.



Anhedonia, a deficit in reward processing, is an endophenotype of several neuropsychiatric conditions. Despite its prevalence and debilitating effects, treatments for anhedonia are lacking, primarily because its underlying mechanisms are poorly understood. Dopamine (DA) has been implicated in anhedonia through its role in reward-related learning; glucocorticoid systems may also be involved in that anhedonia is often preceded by chronic stress.


This study investigated DA and glucocorticoid systems in anhedonia using a rat version of the probabilistic reward task (PRT).


Adult male Wistar rats were trained on the PRT and then tested following: (1) activation or inhibition of DA activity induced by amphetamine (AMPH) or pramipexole (PRAMI) injections, (2) chronic mild stress (CMS), or (3) glucocorticoid system activation (dexamethasone (DEX)) or inhibition (mifepristone (MIFE)).


AMPH increased and PRAMI decreased response bias, pointing to enhanced and diminished reward responsiveness with DA agonism and antagonism, respectively. CMS reduced response bias but only in a subpopulation of rats. DEX also decreased response bias, suggesting that glucocorticoid processes contribute to anhedonia, although glucocorticoid inhibition (MIFE) had no effect. None of the manipulations altered the ability to detect and respond to reward-paired stimuli.


These results confirm a role of DA in anhedonia and elucidate the contribution of the glucocorticoid system to this effect. In addition, chronic stress may interfere with normal DA functioning, leading to impaired reward-related learning in some animals. These findings may direct future treatment of anhedonia by targeting DA and glucocorticoid systems, as well as a possible interaction between the two.

KEYWORDS: CMS; Depression; MDD; Reward; Stress

PMID: 30136143

DOI: 10.1007/s00213-018-5007-4