Discovering the Lost Reward: Critical Locations for Endocannabinoid Modulation of the Cortico–Striatal Loop That Are Implicated in Major Depression

Abstract

Depression, the most prevalent psychiatric disorder in the Western world, is characterized by increased negative affect (i.e., depressed mood, cost value increase) and reduced positive affect (i.e., anhedonia, reward value decrease), fatigue, loss of appetite, and reduced psychomotor activity except for cases of agitative depression. Some forms, such as post-partum depression, have a high risk for suicidal attempts. Recent studies in humans and in animal models relate major depression occurrence and reoccurrence to alterations in dopaminergic activity, in addition to other neurotransmitter systems. Imaging studies detected decreased activity in the brain reward circuits in major depression. Therefore, the location of dopamine receptors in these circuits is relevant for understanding major depression. Interestingly, in cortico–striatal–dopaminergic pathways within the reward and cost circuits, the expression of dopamine and its contribution to reward are modulated by endocannabinoid receptors. These receptors are enriched in the striosomal compartment of striatum that selectively projects to dopaminergic neurons of substantia nigra compacta and is vulnerable to stress. This review aims to show the crosstalk between endocannabinoid and dopamine receptors and their vulnerability to stress in the reward circuits, especially in corticostriatal regions. The implications for novel treatments of major depression are discussed.

Integrating Metabolomics and Network Analysis for Exploring the Mechanism Underlying the Antidepressant Activity of Paeoniflorin in Rats With CUMS-Induced Depression

“…In the present study, CUMS led to a decrease in the sucrose preference rate in SPT and a decrease in total travel distance in OFT, which could be reversed by paeoniflorin. Depression is often related to loss of appetite, fatigue and anhedonia, showing that CUMS-induced changes in these parameters are similar to clinical symptoms of depression ( Goldstein Ferber et al, 2021 ). These results demonstrate that the antidepressant-like effects of paeoniflorin are associated with chronic stress-induced decreased motor activity and anhedonia in rats.…”

Role of Stress-Related Dopamine Transmission in Building and Maintaining a Protective Cognitive Reserve

“…Results from animal or human studies also support the prominent role of dopamine (DA) transmission in developing and stabilizing successful coping strategies [ 12 , 18 , 19 , 20 ]. Conversely, reduced DA transmission has been associated with depressive symptoms, including anhedonia and apathy, which characterize both AD and frontotemporal dementia [ 21 , 22 , 23 , 24 , 25 ]. Moreover, data collected in AD patients and animal models of AD support impaired DA transmission in cognitive impairment, and age-related decline in striatal DA has been associated with the cognitive decline seen in normal aging [ 26 , 27 , 28 , 29 ].…”

Between Action and Emotional Survival During the COVID-19 era: Sensorimotor Pathways as Control Systems of Transdiagnostic Anxiety-Related Intolerance to Uncertainty

“…This is in accordance with classical and well-accepted theories on the human subjective sense of perceived control ( 18 ) and the need for predictability to establish and maintaining control ( 19 ). The process for coping with uncertainty described above also involves aspects of anticipated cost and reward ( 20 ) within the capacity for goal conflict regulation ( 21 ).…”