We use a realistic computational model of dopaminergic neurons in vivo to suggest that ethanol, through its effects on Ih, modifies the temporal structure of the spiking activity. The model predicts that the dopamine level may increase much more during bursting than pacemaking activity, especially in those brain regions with a slow dopamine clearance rate. The results suggest that a selective pharmacological remedy could thus be devised against the rewarding effects of ethanol that are postulated to mediate alcohol abuse and addiction, targeting the specific HCN genes expressed in dopaminergic neurons.
Model Type: Neuron or other electrically excitable cell; Electrogenic pump
Cell Type(s): Substantia nigra pars compacta DA cell
Currents: I Na,t; I A; I K; I K,leak; I h; I Calcium; Na/K pump
Receptors: AMPA; NMDA; Glutamate; Gaba
Transmitters: Dopamine
Model Concept(s): Activity Patterns; Bursting; Active Dendrites; Detailed Neuronal Models; Action Potentials; Pathophysiology; Sodium pump; Alcohol Use Disorder
Simulation Environment: NEURON
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu]
References:
Migliore M, Cannia C, Canavier CC. (2008). A modeling study suggesting a possible pharmacological target to mitigate the effects of ethanol on reward-related dopaminergic signaling. Journal of neurophysiology. 99 [PubMed]