Reinforcement properties of addictive drugs 

To understand addiction we must elucidate the specific traces the drug experience leaves in the brain and how they lead to the development of addiction. Several key synaptic adaptations that occur after single or repetitive exposures to an addictive drug has been studied. 

Repetitive drug use induces changes in the normal circuitry of rewarding and adaptive behaviors, causing in neuroplastic changes that result in recurrent, drug-seeing behaviors; an inability to regulate such behaviors; continued use of drugs despite negative consequences, vulnerability to relapse and reduced drive to acquire biologically relevant natural reward important for survival and optimal functionality. Addictive drugs target the mesocoticolimbic dopamine (DA) system. This system originates in the ventral tegmental area (VTA) and projects mainly to the nucleus accumbens (NAc) and prefrontal cortex (PFC). It has been shown that addictive drugs leave an imprint in glutamatergic and GABAergic synaptic transmission in these three brain areas. Drug-evoked synaptic plasticity outlasts the presence of the drug in the brain and contributes to the reorganization of neural circuits. It is relevant to note that in most cases these early changes are not sufficient to induce the disease, with repetitive drug exposure, they may add up and cause addictive behavior. 

Converging evidence from many studies suggests that addictive drugs modify synaptic transmission in the mesocorticolimbic DA system by hijacking mechanisms normally used for adaptive forms of experience-dependent synaptic plasticity. Addictive drugs have in common that they increase mesolimbic DA levels. First, by reducing transmitter release from inhibitory afferents onto DA neurons, indirectly increasing the firing rate of DA neurons, a mechanism defined as disinhibition (opiods, cannabinoids and benzodiazepines). Second, drugs such as nicotine that directly depolarized DA neurons by activating acetylcholine receptors. Third, by targeting the dopamine transporters –such as psychostimulants.

However, it is important to note that drug exposure alone is necessarily sufficient to elicit synaptic plasticity. On the contrary, many forms of drug-evoked synaptic plasticity appear to depend on the context in which the drug has been experienced, presumably because the final synaptic adaptation will depend both on the molecular action of the drug and the pattern of neural activity in the brain at the time the drug is experienced. Although a single drug experience is certainly not sufficient to induce addiction, the synaptic and neural circuit adaptations caused by a drug experience often persist and lay the foundation upon which further drug-induced adaptations occur.

References 

Brown MTC, Bellone C, Mameli M, Labouèbe G, Bocklisch C, et al. (2010) Drug-Driven AMPA Receptor Redistribution Mimicked by Selective Dopamine Neuron Stimulation. PLoS ONE 5(12): e15870. doi:10.1371/journal.pone.0015870

 Luscher C, Malenka RC (2011) Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit  remodeling. Neuron 69: 650–663