Cannabinoid withdrawal produces a hypofunction of dopaminergic neurons targeting medium spiny neurons (MSN) of the forebrain. Administration of a CB1 receptor antagonist to control rats provoked structural abnormalities, reminiscent of those observed in withdrawal conditions and support the regulatory role of cannabinoids in neurogenesis, axonal growth and synaptogenesis. Experimental observations were incorporated into a realistic computational model which predicts a strong reduction in the excitability of morphologically-altered MSN, yielding a significant reduction in action potential output. These paper provided direct morphological evidence for functional abnormalities associated with cannabinoid dependence at the level of dopaminergic neurons and their post synaptic counterpart, supporting a hypodopaminergic state as a distinctive feature of the “addicted brain”.
Model Type: Dendrite
Region(s) or Organism(s): Basal ganglia
Cell Type(s): Nucleus accumbens spiny projection neuron
Currents: I Na,t; I A; I Potassium; I A, slow; I Krp
Receptors: AMPA
Transmitters: Glutamate
Model Concept(s): Action Potential Initiation; Activity Patterns; Active Dendrites; Detailed Neuronal Models; Action Potentials; Synaptic Integration; Addiction
Simulation Environment: NEURON
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu]
References:
Spiga S, Lintas A, Migliore M, Diana M. (2010). Altered architecture and functional consequences of the mesolimbic dopamine system in cannabis dependence. Addiction biology. 15 [PubMed]