The Bioenergetic Cost of Reward: Thermodynamic Constraints on GPCR-Mediated Signaling as a Substrate for Basal Cognition

The emerging field of basal cognition proposes that decision-making, valence, and reward-like processing are conserved capacities present even in non-neural and unicellular organisms (Lyon et al., 2021; Levin et al., 2021; Reid, 2023). This perspective examines a specific implementation question left open by that framework: whether classical ligand-receptor signaling of the kind mediating dopaminergic transmission in animals — dependent on G-protein-coupled receptors (GPCRs) and their downstream allosteric machinery — could plausibly serve as the substrate for such reward-like computation at the unicellular scale. We argue, from strict bioenergetics and cellular physiology, that it could not. Synthesizing, embedding, and maintaining GPCR-class transmembrane proteins demands continuous, substantial expenditure of ATP. Under the strict energy economy of unicellular organisms or early molecular aggregates, investing metabolic resources in complex modulatory receptors without an integrated architecture to convert that signal into a survival advantage is thermodynamically unjustified. We conclude that the evolutionary complexity of the nervous system produced the specialized machinery required to use dopamine as a computational variable, and that basal-cognition frameworks seeking a molecular substrate for reward-like signaling in single cells must look to cheaper mechanisms than GPCR-mediated transduction — or explain how the bioenergetic cost was met.