Key pathway  

Diagram showing some of the key components of the mesocorticolimbic ("reward")
circuit

**Ventral tegmental area**

* The  ventral tegmental area  (VTA) is important in responding to stimuli and cues that indicate a reward is present. Rewarding stimuli (and all addictive drugs) act on the circuit by triggering the VTA to release dopamine signals to the  nucleus accumbens  , either directly or indirectly.  [ _ citation needed   _ ]  The VTA has two important pathways: The  mesolimbic pathway  projecting to limbic (striatal) regions and underpinning the motivational behaviors and processes, and the _mesocortical pathway_ projecting to the prefrontal cortex, underpinning cognitive functions, such as learning external cues, etc.  [31]
* Dopaminergic neurons in this region converts the amino acid  tyrosine  into DOPA using the enzyme  tyrosine hydroxylase  , which is then converted to dopamine using the enzyme  dopa-decarboxylase ") .  [32]

**Striatum (Nucleus Accumbens)**

* The striatum is broadly involved in acquiring and eliciting learned behaviors in response to a rewarding cue. The VTA projects to the striatum, and activates the GABA-ergic Medium Spiny Neurons via D1 and D2 receptors within the ventral (Nucleus Accumbens) and dorsal striatum.  [33]
* The _Ventral Striatum_ (the Nucleus Accumbens) is broadly involved in acquiring behavior when fed into by the VTA, and eliciting behavior when fed into by the PFC. The NAc shell projects to the pallidum and the VTA, regulating limbic and autonomic functions. This modulates the reinforcing properties of stimuli, and short term aspects of reward. The NAc Core projects to the substantia nigra and is involved in the development of reward-seeking behaviors and its expression. It is involved in spatial learning, conditional response, and impulsive choice; the long term elements of reward.  [31]
* The Dorsal Striatum is involved in learning, the _Dorsal Medial Striatum_ in goal directed learning, and the _Dorsal Lateral Striatum_ in stimulus-response learning foundational to Pavlovian response.  [34]  On repeated activation by a stimuli, the Nucleus Accumbens can activate the Dorsal Striatum via an intrastriatal loop. The transition of signals from the NAc to the DS allows reward associated cues to activate the DS without the reward itself being present. This can activate cravings and reward-seeking behaviors (and is responsible for triggering relapse during abstinence in addiction).  [35]

**Prefrontal Cortex**

* The VTA dopaminergic neurons project to the PFC, activating glutaminergic neurons that project to multiple other regions, including the Dorsal Striatum and NAc, ultimately allowing the PFC to mediate salience and conditional behaviors in response to stimuli.  [35]
* Notably, abstinence from addicting drugs activates the PFC, glutamatergic projection to the NAc, which leads to strong cravings, and modulates reinstatement of addiction behaviors resulting from abstinence. The PFC also interacts with the VTA through the mesocortical pathway, and helps associate environmental cues with the reward.  [35]

**Hippocampus**

* The Hippocampus has multiple functions, including in the creation and storage of memories . In the reward circuit, it serves to contextual memories and associated cues. It ultimately underpins the reinstatement of reward-seeking behaviors via cues, and contextual triggers.  [36]

**Amygdala**

* The AMY receives input from the VTA, and outputs to the NAc. The amygdala is important in creating powerful emotional  flashbulb memories  , and likely underpins the creation of strong cue-associated memories.  [37]  It also is important in mediating the anxiety effects of withdrawal, and increased drug intake in addiction.  [38]