Researchers discovered that dopamine D2 receptors (DRD2s) in cholinergic interneurons (ChINs) play a crucial role in cocaine addiction. The findings were published in Biological Psychiatry, a leading academic journal in the field of psychiatry.

Drug addiction is a mental disorder, 'where' a person obsessively seeks out and uses drugs (narcotics) despite their harmful effects. It can lead to interpersonal conflict and physical health problems, thereby incurring significant social costs. Once consumed, drugs of abuse (e.g. cannabis and cocaine) increase the dopamine* concentration in the brain's reward system and activate dopamine receptors, which, in turn, causes intense craving for drugs.

However, there are individual differences in drug addiction. Some people are more vulnerable to addiction when exposed to similar dose of addictive drug. Yet, the neurobiological mechanism underlying such phenomenon remains elusive.

By applying electrophysiological and optogenetic techniques to cocaine self-administration model, the research team identified DRD2  overexpression in cholinergic interneurons (ChINs) of the nucleus accumbens (NAc) of mice susceptible to addiction.

Addiction-susceptible mice showed an increased level of DRD2 expression and a reduced level of cell activation, which is caused by dopamine D2 receptors expressed excessively in ChINs as the receptor activation reduces ChIN activity.

DRD2 overexpression in ChINs mimicked cocaine-induced effects on the dendritic spine density and the ratios of excitatory inputs between two distinct medium spiny neurons cell-types, while DRD2 depletion precluded cocaine-induced synaptic plasticity.

Through this mechanism, ChINs can affect the activation and synaptic plasticity of downstream medium spiny neurons (which comprise most of the NAc neurons) in diverse ways, thereby causing susceptibility to cocaine addiction.
 
https://view.asiae.co.kr/article/2020052514592305777

https://www.biologicalpsychiatryjournal.com/article/S0006-3223(20)31588-2/pdf