Figure 1.
Diagram of glutamatergic neurocircuits within the mesocorticolimbic system (blue hexagonals and associated arrows), extended amygdala (red rectangles and associated arrows) as well as related memory (green circles and associated arrows) and limbic structures involved in the development of alcohol/drug dependence. The early experimentation/intoxication stage of alcohol/drug abuse is marked by neuroplastic changes in the mesocorticolimbic system. Later, the extended amygdala plays an increasingly greater role, relative to the mesocorticolimbic system (although these systems interact as seen in this Figure), in mediating continued alcohol/drug usage despite physical, emotional, social and/or economic consequences. In later stages of alcohol dependence, most of the neuroplastic changes to the mesocorticolimbic and extended amygdala systems attributed to repeated cycles of alcohol/drug abuse—withdrawal—and relapse have already occurred. While associative learning, contextual conditioning, and habit formation have been occurring throughout the addiction cycle, highlighted are these multiple memory systems (that interact and often overlap) which experience a substantial increase in glutamatergic activity-mediated neuroplastic changes. Basic descriptors of the memory processes mediated by the hippocampus and caudate-putamen, as well as the stages of relapse they influence, are also indicated. ACB, Nucleus Accumbens; AMYG, Amygdala; BNST, Bed Nucleus of the Stria Terminalis; CPU, Caudate Putamen; CTX, Cortex; HIPP, Hippocampus; MDTN, Medial Dorsal Thalamic Nucleus; ML, Mesolimbic; mPFC, Medial Prefrontal Cortex; VTA, Ventral Tegmental Area.