Units of dendritic branches called dendritic spines represent more than simply decorative appendages of the neuron and actively participate in integrative functions of "spinous" nerve cells thereby contributing to the general phenomenon of synaptic plasticity. In animal models of drug addiction, spines are profoundly affected by treatments with drugs of abuse and represent important sub cellular markers which interfere deeply into the physiology of the neuron thereby providing an example of the burgeoning and rapidly increasing interest in "structural plasticity". Medium Spiny Neurons (MSNs) of the Nucleus Accumbens (Nacc) show a reduced number of dendritic spines and a decrease in TH-positive terminals upon withdrawal from opiates, cannabinoids and alcohol. The reduction is localized "strictly" to second order dendritic branches where dopamine (DA)-containing terminals, impinging upon spines, make synaptic contacts. In addition, long-thin spines seems preferentially affected raising the possibility that cellular learning of these neurons may be selectively hampered. These findings suggest that dendritic spines are affected by drugs widely abused by humans and provide yet another example of drug-induced aberrant neural plasticity with marked reflections on the physiology of synapses, system structural organization, and neuronal circuitry remodeling.