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The mesolimbic pathway, also known as the reward pathway, is a dopaminergic pathway in the brain.
The mesolimbic pathway regulates incentive salience, motivation, reinforcement learning, and fear, among other cognitive processes.
The mesolimbic pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain.
The ventral striatum includes the nucleus accumbens and the olfactory tubercle.
The release of dopamine from the mesolimbic pathway into the nucleus accumbens regulates incentive motivation and desire for rewarding stimuli and facilitates reinforcement, reward-related motor function learning, and perception of pleasure.
Dysregulation of the mesolimbic pathway and its output neurons in the nucleus accumbens has a significant role in the development and maintenance of an addiction.
The mesolimbic pathway is a collection of dopaminergic neurons that project from the ventral tegmental area (VTA) to the ventral striatum, which includes the nucleus accumbens (NAcc) and olfactory tubercle.
The mesolimbic pathway is a medial forebrain neural pathway bundle that mediates brain stimulation reward.
The VTA is located in the midbrain and consists of dopaminergic, GABAergic, and glutamatergic neurons.
Dopaminergic neurons in the VTA receive stimuli from both cholinergic neurons in the pedunculopontine nucleus and the laterodorsal tegmental nucleus as well as glutamatergic neurons in other regions such as the prefrontal cortex.
The nucleus accumbens and olfactory tubercle are located in the ventral striatum and are primarily composed of medium spiny neurons.
The nucleus accumbens is subdivided into limbic and motor subregions: NAcc shell and NAcc core.
The medium spiny neurons in the nucleus accumbens receive input from both the dopaminergic neurons of the VTA and the glutamatergic neurons of the hippocampus, amygdala, and medial prefrontal cortex.
The medium spiny neurons’ projections release GABA onto the ventral pallidum.
The mesolimbic pathway is involved in motivation cognition.
Depletion of dopamine in this pathway, or lesions at its site of origin, decrease the extent to which one’s willing to go to obtain a
Dopaminergic drugs increase the extent one is willing to go to obtain a reward.
Moreover, the firing rate of neurons in the mesolimbic pathway increases during anticipation of reward, which may explain craving.
Mesolimbic dopamine release
has only a minor or secondary role in pleasure perception.
The mesolimbic pathway output neurons, D1-type medium spiny neurons, within the nucleus accumbens play a central role in the neurobiology of addiction.
Drug addiction induces chemical changes in the brain’s circuitry.
Abused substances: cocaine, alcohol, amphetamine and nicotine increase extracellular levels of dopamine within the mesolimbic pathway, preferentially within the nucleus accumbens.
Cocaine precludes the re-uptake of synaptic dopamine by blocking the presynaptic dopamine transporter.
Amphetamines promote increased dopamine from the synaptic vesicles.
Non-stimulant drugs typically bind with ligand-gated channels or G protein-coupled receptors: alcohol, nicotine, and tetrahydrocannabinol (THC).
These dopaminergic activations of the mesolimbic pathway is associated
with the perception of reward.
This stimulus-reward association is resistant to extinction and creates an increased motivation to repeat that same behavior that caused it.
Abusive emotional, physical, and sexual experiences and adverse life events are associated with a heightened limbic response to cocaine.
Individuals who have previously suffered abuse were more likely to have a brain pathway primed for cocaine or drug use.
The mesolimbic pathway is implicated in schizophrenia, depression, and Parkinson’s disease, and is implicated
in overuse of digital media.