Journal of Depression and Anxiety
Open Access

Abstract

An Insight into the Cellular Mechanisms of Addiction to Psychostimulants

Ashim Kumar Basak and Tridip Chatterjee

Natural rewards like food, sex etc are evaluated as pleasureable elements or essential for the survival of a mammal due to the interaction of dopamine (DA) released by ventral tegmental area (VTA) on nucleus accumbens (NAc) and other targets in an interconnected neuronal network in brain called ‘reward circuit. Psychostimulants induce prolonged and much greater interaction of DA with its targets and develop the drug related memory in lieu of the memories of natural rewards and induce motor activities required for drug acquisition. Long term potentiation (LTP), a major contributor of synaptic plasticity, occurs in many components of the reward circuit due to both acute and chronic drug exposures, resulting in the morphological changes of neurons that may underlie drug related memory acquisition. Potentiation may occur in VTA DA neurons, medium spiny neurons (MSNs) of NAc, prefrontal cortical (PFC) neurons etc. making the probability that glutamate release from PFC will be increased and VTA DA neurons and MSNs will more effectively interact with the released glutamate. The overall result is that ventral pallidum (VP), the main executor of motor behavior, will be disinhibited for initiating motor action via the inhibition of NAc. Finally a situation may arrive when merely a cue associated with the drug used can provoke a subject to seek drug possibly via gluamatergic action of potentiated PFC on NAc. Relapse of psychostimulant seeking behavior after a prolonged withdrawal is mediated by the potentiation of amygdala (Ag) and PFC also contributes to it.