Muscarinic acetylcholine receptors expressed in the central nervous system mediate various functions, including cognition, memory, or reward. Therefore, muscarinic receptors represent potential pharmacological targets for various diseases and conditions, such as Alzheimer's disease, schizophrenia, addiction, epilepsy, or depression. Muscarinic receptors are allosterically modulated by neurosteroids and steroid hormones at physiologically relevant concentrations. In this review, we focus on the modulation of muscarinic receptors by neurosteroids and steroid hormones in the context of diseases and disorders of the central nervous system. Further, we propose the potential use of neuroactive steroids in the development of pharmacotherapeutics for these diseases and conditions.

• Klíčová slova
• Alzheimer’s disease, Parkinson’s disease, cholesterol, depression, muscarinic receptors, neuroactive steroids, neurosteroids, schizophrenia, substance abuse,
• MeSH
• centrální nervový systém MeSH
• cholinergní látky MeSH
• hormony MeSH
• neurosteroidy * farmakologie   MeSH
• receptory muskarinové MeSH
• steroidy farmakologie   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cholinergní látky MeSH
• hormony MeSH
• neurosteroidy * MeSH
• receptory muskarinové MeSH
• steroidy MeSH

Tight interactions exist between dopamine and acetylcholine signaling in the striatum. Dopaminergic neurons express muscarinic and nicotinic receptors, and cholinergic interneurons express dopamine receptors. All neurons in the striatum are pacemakers. An increase in dopamine release is activated by stopping acetylcholine release. The coordinated timing or synchrony of the direct and indirect pathways is critical for refined movements. Changes in neurotransmitter ratios are considered a prominent factor in Parkinson's disease. In general, drugs increase striatal dopamine release, and others can potentiate both dopamine and acetylcholine release. Both neurotransmitters and their receptors show diurnal variations. Recently, it was observed that reward function is modulated by the circadian system, and behavioral changes (hyperactivity and hypoactivity during the light and dark phases, respectively) are present in an animal model of Parkinson's disease. The striatum is one of the key structures responsible for increased locomotion in the active (dark) period in mice lacking M4 muscarinic receptors. Thus, we propose here a hierarchical model of the interaction between dopamine and acetylcholine signaling systems in the striatum. The basis of this model is their functional morphology. The next highest mode of interaction between these two neurotransmitter systems is their interaction at the neurotransmitter/receptor/signaling level. Furthermore, these interactions contribute to locomotor activity regulation and reward behavior, and the topmost level of interaction represents their biological rhythmicity.

• Klíčová slova
• addiction, biological rhythm, dopamine receptors, locomotor activity, muscarinic receptors, striatum,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH