Biology Reference
In-Depth Information
Chapter 7
S YNAPTIC P LASTICITY IN C OCAINE A DDICTION
Margarida Corominas 1, * , Carlos Roncero 1 , Xavier Castells 2
and Miquel Casas 1
1 Department of Psychiaty, Vall d'Hebron Universitary Hospital,
Universitat Autonoma of Barcelona, Barcelona, Spain.
2 Department of Pharmacology, Vall d'Hebron Universitary Hospital,
Universitat Autonoma of Barcelona, Barcelona, Spain
A BSTRACT
Addiction has been described as a pathological usurpation of the neuronal mechanisms
involved in reward, motivation and reinforcement. Nevertheless, environmental stimuli
closely associated with the drug can acquire the ability to elicit the emotional responses
that were induced by the drug. From this perspective, addiction has something to do with
long-term associative learning and memory. These effects induced by cocaine
consumption account for the chronic relapse which characterizes addiction. Long-term
potentiation (LTP) and long-term depression (LTD) are forms of synaptic plasticity by
which chronic cocaine induces changes in the mesocorticolimbic system primarily
through dopamine and glutamate transmission. Recent evidence suggests that brain-
derived neurotrophic factor (BDNF) and its intracellular pathways are involved in the
molecular mechanisms that modify synaptic plasticity underlying addiction.
A single dose of cocaine induces an enhancement in locomotor activity that correlates
with an increase in synaptic strength (the ratio AMPAR/NMDAR) in the VTA. This
effect was not increased after repeated cocaine doses, indicating that cocaine-induced
synaptic plasticity in the VTA is transient and also has a ceiling effect. Adaptations in
downstream circuitry, such the nucleus accumbens (NAc), are likely to be more
important for the longer-lasting behavioral changes associated with drug addiction. EPSC
is decreased (LTD was induced) at synapses made by prefrontal cortical afferents in
spiny neurons of the NAc shell, but not in the core. This inhibitory effect appears to be
induced by D1 receptor activation. These changes in synaptic plasticity disrupt goal-
* Phone: +34 (93) 489 4294 / +34 (93) 489 4295. Fax: +34 (93) 489 4587 e-mail: mcoromin@vhebron.net
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