Editing Ventral tegmental area (section)

=== Drug addiction ===
{{Hatnote|Main section: [[Addiction#Reward system|Addiction § Reward system]]}}
The nucleus accumbens and the ventral tegmental area are the primary sites where [[addiction|addictive]] [[drug]]s act. The following are commonly considered to be addictive: [[cocaine]], [[alcohol (drug)|alcohol]], [[opioids]], [[nicotine]], [[cannabinoids]], and [[amphetamine]] and its analogs. These drugs alter the neuromodulatory influence of dopamine on the processing of reinforcement signals by prolonging the action of dopamine in the nucleus accumbens or by stimulating the activation of neurons there and also in the VTA. The most common drugs of abuse stimulate the release of dopamine, which creates both their rewarding and the psychomotor effects. Compulsive drug-taking behaviors are a result of the long-lasting or permanent<ref>{{Cite journal |last=Powledge |first=Tabitha M. |date=1999 |title=Addiction and the brain |url=https://academic.oup.com/bioscience/article-lookup/doi/10.2307/1313471 |journal=BioScience |language=en |volume=49 |issue=7 |pages=513–519 |doi=10.2307/1313471 |jstor=1313471 |issn=1525-3244}}</ref><ref>{{Cite journal |last1=Bechara |first1=Antoine |last2=Berridge |first2=Kent C. |last3=Bickel |first3=Warren K. |last4=Morón |first4=Jose A. |last5=Williams |first5=Sidney B. |last6=Stein |first6=Jeffrey S. |date=2019 |title=A Neurobehavioral Approach to Addiction: Implications for the Opioid Epidemic and the Psychology of Addiction |journal=Psychological Science in the Public Interest |language=en |volume=20 |issue=2 |pages=96–127 |doi=10.1177/1529100619860513 |issn=1529-1006 |pmc=7001788 |pmid=31591935}}</ref> functional changes in the mesolimbic dopamine system arising from repetitive dopamine stimulation. Molecular and cellular adaptations are responsible for a sensitized dopamine activity in the VTA and along the mesolimbic dopamine projection in response to drug abuse. In the VTA of addicted individuals, the activity of the dopamine-synthesizing enzyme [[tyrosine hydroxylase]] increases, as does the ability of these neurons to respond to excitatory inputs. The latter effect is secondary to increases in the activity of the transcription factor CREB and the up regulation of GluR1, an important subunit of AMPA receptors for glutamate. These alterations in neural processing could account for the waning influence of adaptive emotional signals in the operation of decision making faculties as drug-seeking and drug-taking behaviors become habitual and compulsive.

Experiments in rats have shown that they learn to press a lever for the administration of [[stimulant|stimulant drugs]] into the posterior VTA more readily than into the anterior VTA. Other studies have shown that microinjections of dopaminergic drugs into the nucleus accumbens shell [[hyperlocomotion|increase locomotor activity]] and [[exploration|exploratory behavior]]s, conditioned approach responses, and anticipatory sexual behaviors.

The [[drug withdrawal|withdrawal]] phenomenon occurs because the deficit in reward functioning initiates a distress cycle wherein the drugs become necessary to restore the normal homeostatic state. Recent research has shown that even after the final stages of withdrawal have been passed, drug-seeking behavior can be restored if exposed to the drug or drug-related stimuli.<ref>{{Cite journal |last1=Fuchs |first1=R.A. |last2=Lasseter |first2=H.C. |last3=Ramirez |first3=D.R. |last4=Xie |first4=X. |date=2008 |title=Relapse to drug seeking following prolonged abstinence: the role of environmental stimuli |journal=Drug Discovery Today: Disease Models |volume=5 |issue=4 |pages=251–258 |doi=10.1016/j.ddmod.2009.03.001 |issn=1740-6757 |pmc=2794206 |pmid=20016771}}</ref><ref>{{Cite journal |last=Sinha |first=Rajita |date=2008 |title=Chronic Stress, Drug Use, and Vulnerability to Addiction |journal=Annals of the New York Academy of Sciences |volume=1141 |issue=1 |pages=105–130 |doi=10.1196/annals.1441.030 |issn=0077-8923 |pmc=2732004 |pmid=18991954|bibcode=2008NYASA1141..105S }}</ref><ref>{{Cite journal |last1=Koob |first1=George F. |last2=Volkow |first2=Nora D. |date=2010 |title=Neurocircuitry of Addiction |journal=Neuropsychopharmacology |language=en |volume=35 |issue=1 |pages=217–238 |doi=10.1038/npp.2009.110 |pmid=19710631 |issn=1740-634X|pmc=2805560 }}</ref>