title: Hyperbolic discounting may be reduced to electrical coupling in dopaminergic neural circuits.
abstract: Loss of self-control in drug addicts (e.g. cocaine and amphetamine dependent patients) has been associated with hyperbolic discounting of delayed rewards (i.e., inconsistency in intertemporal choice). Neurobiophysical mechanisms underlying hyperbolic discounting are still unknown in spite of recent extensive work in neuroeconomics. Understanding of neuronal mechanisms of hyperbolic discounting is important for establishing neuropharmacological treatment of addiction. At the cognitive level, previous studies have indicated that psychophysics of time-estimation (i.e., Weber-Fechner law and Steven's power law of time-perception) may explain inconsistency in intertemporal choice. Regarding neuronal substrates of time-estimation, drugs of abuse dramatically change time-estimation, indicating that dopaminergic activities may mediate time-estimation. With respect to neuronal changes induced by drugs of abuse, recent studies have revealed that gap junction proteins (e.g., connexin 36) in dopamine neurons are increased by an self-administration of dopaminergic drugs such as cocaine and amphetamine. However, it has been yet to be examined how the enhanced electrical coupling due to substance administration induces addiction. Furthermore, a recent biophysical modelling study has demonstrated that the effect of the psychophysical laws are potentiated by non-synaptic electrical coupling between neurons via gap junctions. Based on these current findings, we hypothesized that hyperbolic discounting may be reduced to biophysical characteristics of dopamine neural circuits, that is, electrical coupling between time-encoding dopaminergic neurons via gap junctions. The present hypothesis states that drugs of abuse may induce addiction by exacerbating subject's impulsivity (a discount rate) and inconsistency (hyperbolicity) in intertemporal choice partly due to enhanced expression of gap junction proteins in dopaminergic neurons. Possible psychopharmacological treatments of impulsivity in drug addicts implied by our present hypothesis, e.g., administration of a gap junction blocker, are discussed.
authors.affiliation: Department of Cognitive and Behavioral Science, The University of Tokyo, Graduate School of Arts and Sciences, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan. taiki@ecs.c.u-tokyo.ac.jp
authors.forename: Taiki
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002755:Choice Behavior / Q000187:drug effects*; D003192:Compulsive Behavior / Q000503:physiopathology*; D006801:Humans; D008959:Models, Neurological; D009294:Narcotics / Q000009:adverse effects; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D011954:Receptors, Dopamine / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
chemical_list: D009294:Narcotics; D011954:Receptors, Dopamine