An abundance of data points to a relatively circumscribed set of brain structures as central to addiction. The ventral tegmental area (VTA) is a midbrain nucleus composed of dopamine and GABA-producing cells. A review of database suggests that the initiation of addictive processes occur in the VTA. The VTA projects DA efferents broadly, but the targets important for stress and addiction are primarily the nucleus accumbens (NAc), prefrontal cortex (PFC), and certain amygdaloid nuclei. Other critical structures include the hippocampus and pedunculopontine nucleus (PPN). The nucleus accumbens projects GABA-ergic efferents to the VTA and PFC. The PFC projects excitatory, glutamatergic efferents to the NAc and VTA. The balance of the synaptic and neuromodulatory outputs of each of these nuclei is critical for acquisition and maintenance of addiction. This chapter scrutinizes these pathways and their modulation by the stress response. A critical shift in understanding the mechanisms of addiction follow the recognition that these circuits are modulated in response to both rewards such as juice, cocaine, amphetamine, and nicotine, as well as distress. Interestingly, this reward circuit is active in the human response to monetary gain and even laughter. A painful experience, such as a divorce, might act in the same way for an addict as a pleasurable one, such as a dose of morphine-both are experienced by the brain as highly important and salient.
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