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Highly simplified scheme of some common, chronic actions of drugs of abuse on the VTA–NAc circuit. The top panel (Control) shows a VTA dopamine
neuron innervating an NAc GABA neuron, and glutamatergic inputs to the VTA and NAc neurons, under normal conditions. After chronic drug
administration, several adaptations occur. In the VTA, drug exposure induces tyrosine hydroxylase (TH) and increases AMPA glutamatergic responses,
possibly via induction of GluA1 and altered trafficking of AMPA receptors. As well, VTA dopamine neurons decrease in size in response to opiates or
cannabinoids but not other drugs of abuse. In the NAc, all drugs of abuse induce the transcription factor ΔFosB, which may then mediate some of the
shared aspects of addiction via regulation of numerous target genes. Several, but not all, drugs of abuse also induce CREB activity in this region, which
Source: Reinforcement and Addictive Disorders, Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 3e
may be mediated via upregulation of the cAMP pathway. Several additional changes have been found for stimulant exposure. Stimulants induce timeCitation:inNestler
Hyman SE, responses
Holtzman DM,
Malenka
RC. Molecular
Neuropharmacology:
A Foundation
for ClinicalofNeuroscience,
3e; or
2015
dependent changes
AMPAEJ,
glutamatergic
in NAc
neurons,
possibly mediated
via altered trafficking
or expression
AMPA subunits
of
Available
at:
http://mhmedical.com/
Accessed:
May
11,
2017
several postsynaptic density proteins (eg, PSD95, Homer-1). These changes in postsynaptic glutamate responses are associated with complex changes in
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McGraw-Hill
Education.
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glutamatergicCopyright
innervation
of the
NAc, effects
mediated
in partreserved
via upregulation of AGS3 (activator of G protein signaling) in cortical neurons and
downregulation of the cystine–glutamate transporter (system x−c) in glia in response to stimulants. Stimulants and nicotine also induce dendritic outgrowth