Virtue, Vice, & Addiction

  Schematic of Brain Neurocircuitry








ONE theory and model of neurotransmitters and neural adaptations involved in addiction. Simply put, the development of addiction occurs when neuronal projections from the ventral tegmental area (VTA) increase dopamine signaling within the pleasure sensing nucleus accumbens. This pathway is reinforced through repeated exposures to the substance, which causes the prefrontal cortex to learn and eventually repeat the behavior that led to the neurotransmitter release.

The neural circuits of the VTA, nucleus accumbens, and prefrontal cortex are critical in learning both natural and addictive behavior. Here is a closer look at the neurocircuitry of addiction and how dopamine and glutamate are key neurotransmitters involved:

1. Upon exposure to a naturally rewarding stimulus or a drug, there is an increase in dopamine signaling from the VTA to the nucleus accumbens. The nucleus accumbens ‘perceives’ this dopamine signal and measures the ‘goodness’ of the reward based upon the size of the dopamine release.

2. Glutamate projections from the nucleus accumbens instruct the prefrontal cortex to remember the environment and behaviors which lead to the occurrence of ‘goodness’.

3. Excess signaling of glutamate neurons in the prefrontal cortex stimulates the nucleus accumbens, triggering addiction-seeking behaviors at the expense of naturally rewarding behaviors.

Addiction occurs as the result of dopamine signaling in the nucleus accumbens, and glutamate projections from the prefrontal cortex are key plays in drug seeking and relapse. Glutamate and dopamine both play roles in addiction, and assessing imbalances can help successfully treat addictive behaviors.



Neurocircuitry schematic illustrating the combination of neuroadaptations in the brain circuitry for the three stages of the addiction cycle that drive drug-seeking behavior in the addicted state. Note the activation of the ventral striatum/dorsal striatum in the binge intoxication stage. During the withdrawal–negative-affect stage, the dopamine systems are compromised and brain stress systems such as CRF are activated to reset further the salience of drugs and drug-related stimuli in the context of an aversive dysphoric state. During the preoccupation–anticipation stage, contextual cues via the hippocampus and stimuli cues via the basolateral amygdala converge with frontal cortex activity to drive drug seeking. Other components in the frontal cortex are compromised, producing deficits in executive function.
SOURCE: Koob et al. 2008.


OPIATE RECEPTORS in the Central Nervous System





OPIATE RECEPTORS in Synaptic Junctions

Summary of opioid receptor signaling. Figure depicts opioid receptor signal transduction and trafficking. In general, all four opioid receptor subtypes (mu [μ], delta [δ], kappa [κ], and opioid receptor like-1 [ORL1]) share these common pathways. New research indicates that selective ligands at each opioid receptor can direct opioid receptors to favor one or more of these signaling events (biased agonism or ligand-directed signaling). Arrows refer to activation steps; T lines refer to blockade or inhibition of function. βγ = G protein β-γ subunit; cAMP = cyclic adenosine monophosphate; ERK = extracellular signal-regulated kinase; JNK = c-jun N-terminal kinase; MAPK = mitogen-activated protein kinases; P = phosphorylation.









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