Abstract
Mesencephalic dopaminergic neurons were suggested to be a critical physiopathology substrate for addiction disorders. Among neuroadaptive processes to addictive drugs, structural plasticity has attracted attention. While structural plasticity occurs at both pre- and post-synaptic levels in the mesolimbic dopaminergic system, the present review focuses only on dopaminergic neurons. Exposures to addictive drugs determine two opposite structural responses, hypothrophic plasticity produced by opioids and cannabinoids (in particular during the early withdrawal phase) and hypertrophic plasticity, mostly driven by psychostimulants and nicotine. In vitro and in vivo studies identified BDNF and extracellular dopamine as two critical factors in determining structural plasticity, the two molecules sharing similar intracellular pathways involved in cell soma and dendrite growth, the MEK-ERK1/2 and the PI3K-Akt-mTOR, via preferential activation of TrkB and dopamine D3 receptors, respectively. At present information regarding specific structural changes associated to the various stages of the addiction cycle is incomplete. Encouraging neuroimaging data in humans indirectly support the preclinical evidence of hypotrophic and hypertrophic effects, suggesting a possible differential engagement of dopamine neurons in parallel and partially converging circuits controlling motivation, stress, and emotions.
Highlights
Structural plasticity in neurons can be defined as a series of measurable changes in the morphologically defined components of the neuron, i.e., numbers, size, and composition of soma, dendrites, axons, and synapses, occurring over time and in response to changes in the cell environment
Pharmacologic agents characterized by their addictive properties, for example psychostimulants, opioids, nicotine, cannabinoids, and alcohol, were found to engage dopaminergic neurons of the mesocorticolimbic contingent located in the ventral tegmental area (VTA) (Koob, 1992; Di Chiara, 1995; Koob and Le Moal, 2005; Chen et al, 2010)
In this article we summarize the evidence of structural plasticity occurring in mesencephalic dopaminergic neurons following exposure to addictive drugs, focusing on soma, and dendritic arborization rather than synapses and addressing the key molecular intracellular signaling involved
Summary
Structural plasticity in neurons can be defined as a series of measurable changes in the morphologically defined components of the neuron, i.e., numbers, size, and composition of soma, dendrites, axons, and synapses, occurring over time and in response to changes in the cell environment. In this article we summarize the evidence of structural plasticity occurring in mesencephalic dopaminergic neurons following exposure to addictive drugs, focusing on soma, and dendritic arborization rather than synapses and addressing the key molecular intracellular signaling involved.
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