Spontaneous Adenosine and Dopamine Cotransmission in the Caudate-Putamen Is Regulated by Adenosine Receptors

Abstract

Transient changes in adenosine and dopamine have been measured in vivo, but no studies have examined if these transient changes occur simultaneously. In this study, we characterized spontaneous adenosine and dopamine transients in anesthetized mice, examining coincident release in the caudateputamen for the first time. We found that in C57B mice, most of the dopamine transients (77%) were coincident with adenosine, but fewer adenosine transients (12%) were coincident with a dopamine transient. On average, the dopamine transient started 200 ms before its coincident adenosine transient, so they occurred concurrently. There was a positive correlation (r = 0.7292) of adenosine and dopamine concentrations during coincident release. ATP is quickly broken down to adenosine in the extracellular space, and the coincident events may be due to corelease, where dopaminergic vesicles are packaged with ATP, or cotransmission, where ATP is packaged in different vesicles released simultaneously with dopamine. The high frequency of adenosine transients compared to that of dopamine transients suggests that adenosine is also released from nondopaminergic vesicles. We investigated how A 1 and A 2A adenosine receptors regulate adenosine and dopamine transients using A 1 and A 2A KO mice. In A 1 KO mice, the frequency of adenosine and dopamine transients increased, while in A 2A KO mice, the frequency of adenosine alone increased. Adenosine receptors modulate coincident transients and could be drug targets to modulate both dopamine and adenosine release. Many spontaneous dopamine transients have coincident adenosine release, and regulating adenosine and dopamine cotransmission could be important for designing treatments for dopamine diseases, such as Parkinson's or addiction.

Dynamic and Rapid Detection of Guanosine during Ischemia

“…This behavior is indicative of the negative feedback effects of an inhibitory autoreceptor with a high activation threshold. Guanosine is currently considered an orphan neuromodulator; while significant evidence for a guanosine-specific receptor has been established, the precise receptor has yet to be identified. , Adenosine’s A 1 receptor is well known for its inhibitory effects and has been demonstrated to negatively regulate rapid adenosine release. − Guanosine can interact nonspecifically at the A 1 receptor to activate a variety of neuroprotective pathways; however, abolition of adenosine receptors does not fully abolish guanosine’s protective impact, suggesting a role for its individual receptor. ,, …”

Recent Advances in the Development and Characterization of Electrochemical and Electrical Biosensors for Small Molecule Neurotransmitters

“…This, in turn, yields important insight about coincident biological processes that continues to drive the field forward. For example, Borgus et al detected transient dopamine and adenosine simultaneously with FSCV and a bare CFME in vivo (Figure ). This is the first example of dual detection of spontaneous adenosine and dopamine, providing valuable insight on how adenosine can impact dopamine concentrations.…”

“…For example, Borgus et al detected transient dopamine and adenosine simultaneously with FSCV and a bare CFME in vivo (Figure ). This is the first example of dual detection of spontaneous adenosine and dopamine, providing valuable insight on how adenosine can impact dopamine concentrations. This example of multiplex detection was possible due to the different oxidation potentials of dopamine and adenosine and due to the unique CV shape of adenosine, making it distinguishable from other neurotransmitter signals.…”

“…(ii) Amperometric trace of adenosine and dopamine detection. Adapted with permission from ref , Copyright 2021 American Chemical Society.…”

Maximizing Electrochemical Information: A Perspective on Background-Inclusive Fast Voltammetry

“…For almost four decades, background subtraction has been de rigueur in fast voltammetry (e.g., FSCV, , FSCAV, FCSWV). Today, even the smallest stimulus peaks associated with endogenous transients can be readily identified by fast voltammetry and related techniques with modern data acquisition and analysis capabilities. − …”