The role of nicotinic cholinergic neurotransmission in delusional thinking

Abstract

Delusions are a difficult-to-treat and intellectually fascinating aspect of many psychiatric illnesses. Although scientific progress on this complex topic has been challenging, some recent advances focus on dysfunction in neural circuits, specifically in those involving dopaminergic and glutamatergic neurotransmission. Here we review the role of cholinergic neurotransmission in delusions, with a focus on nicotinic receptors, which are known to play a part in some illnesses where these symptoms appear, including delirium, schizophrenia spectrum disorders, bipolar disorder, Parkinson, Huntington, and Alzheimer diseases. Beginning with what we know about the emergence of delusions in these illnesses, we advance a hypothesis of cholinergic disturbance in the dorsal striatum where nicotinic receptors are operative. Striosomes are proposed to play a central role in the formation of delusions. This hypothesis is consistent with our current knowledge about the mechanism of action of cholinergic drugs and with our abstract models of basic cognitive mechanisms at the molecular and circuit levels. We conclude by pointing out the need for further research both at the clinical and translational levels.

Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model

“…Dopamine neurotransmission is involved in motor control, cognition and emotion, and this neurotransmitter dysregulated levels could be related to the behavioral alterations observed in the infection. In addition, dopamine dysfunction is associated with neuropsychiatric disorders like schizophrenia spectrum disorders ( Caton et al., 2020 ; Eyles et al., 2012 ).…”

Morphological and biochemical repercussions ofToxoplasma gondiiinfection in a 3D human brain neurospheres model

“…Dopamine neurotransmission is involved in motor control, cognition and emotion, and dysregulated levels of this neurotransmitter could be related to the behavioral alterations observed in T. gondii infection. In addition, dopamine dysfunction is associated with neuropsychiatric disorders like schizophrenia spectrum disorders (40,64).…”

“…Nicotinic cholinergic neurotransmission may also play a role in schizophrenia spectrum disorders and other psychiatric illnesses (64). Neuroinflammation mediated by T. gondii also promotes chemokines and growth factors release.…”

Medicinal Chemistry of Indane and Its Analogues: A Mini Review

“…Primarily, the activity of AChE declines with the severity of dementia, whereas the BuChE activity enhances under same conditions. Both AChE and BuChE differ in substrate specificity, enzyme kinetics, and expression in various regions of the brain and play a key role in regulating the acetylcholine (Ach)‐mediated neurotransmission [61] . The enzymes play role in modulating the regional cerebral blood flow, phosphorylation of tau proteins, and regulates the amyloid cascade that significantly influence the rate of progression of the Alzheimer disease [62] .…”