NAcc medium spiny neuron: effects of cannabinoid withdrawal (Spiga et al. 2010)

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”.
1 . 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(3):266-76 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Dendrite;
Brain Region(s)/Organism: Basal ganglia;
Cell Type(s): Nucleus accumbens spiny projection neuron;
Channel(s): I Na,t; I A; I Potassium; I A, slow; I Krp;
Gap Junctions:
Receptor(s): AMPA;
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Activity Patterns; Active Dendrites; Detailed Neuronal Models; Action Potentials; Synaptic Integration; Addiction;
Implementer(s): Migliore, Michele [Michele.Migliore at];
Search NeuronDB for information about:  AMPA; I Na,t; I A; I Potassium; I A, slow; I Krp; Glutamate;
kaf.mod *
kas.mod *
krp.mod *
naf.mod *
fixnseg.hoc *
NEURON mod files from the paper:

Altered architecture and functional consequences of the mesolimbic
dopamine system in cannabis dependence.

Saturnino Spiga, Alessandra Lintas, Michele Migliore and Marco Diana
Addiction Biology, in press, 2010.

The simulation files control.hoc and after-withdrawal.hoc generate the
first 4 sec of the simulations in Fig. 7b top and bottom of the paper,
respectively.  They reproduce the simulations shown in the
supplementary movie.  In the figure is plotted the range 5<t<10
sec from 15 sec long simulations.

Questions on how to use this model should be directed to

Example Usage:

Auto-launch from ModelDB or download and extract the archive, compile
the mod files and start with either double clicking the mosinit.hoc
file (windows), drag and dropping the mosinit.hoc file on the nrngui
icon (mac OS X), or typing "nrngui mosinit.hoc" on the command line

Once the simulation is started pressing the "control" button should
result in the following graph similar to figure Fig. 7b top:


Note if the above graph is resized it looks more like the paper fig.:


20111122 Updated for NEURON 7.2: the MCellRan4 seeds were set < 2^32.