Biology Reference
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ratio was computed. If LTP were induced, a change in the relative contribution of AMPARs
and NMDARs to EPSCs would reflect an increase in AMPAR function or number. Mice
injected with cocaine exhibited a significantly greater AMPAR/NMDAR ratio, than mice
injected with saline. These results demonstrated that cocaine can induce LTP that is related to
an increase in the expression of AMPAR through NMDA mechanisms in dopamine neurons
in the midbrain VTA (Ungless et al., 2001). According to these results, plasticity occurs in
reward related regions of the brain, strengthening synaptic contacts on dopamine neurons and
modifying its functions. There is evidence that these neuronal changes are responsible for
behavioral sensitization, one of the animal models of drug addiction (Kalivas, 1995; Wolf,
1998). Consequently, a wide range of behaviors related to drug abuse such as sensitization of
the incentive-motivational system, can also be affected (Robinson and Berridge, 1993;
Kalivas, 1995). These results indicate that synaptic plasticity at excitatory synapses on
dopamine cells may be a key neural adaptation contributing to the development of addiction.
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To better understand synaptic plasticity and its cellular and molecular correlates, it is
important to explore the evidence that neural changes are induced in addicts after cocaine
abuse. Functional neuroimaging techniques have been very useful in this area and have
provided evidence for the existence of neuroplastic changes involving cortical and subcortical
circuitry in human addicts.
Positron emission tomography (PET) or single photon emission computed tomography
(SPECT) studies have been performed in addicts during periods of abstinence. The aim of
these studies was to explore the effects of repeated
cocaine use in the brain. Some of these
studies have assessed, at the same time, the behavioral and emotional consequences of
cocaine abuse during active use and abstinence.
Volkow et al. (1992) studied 21 patients receiving treatment for cocaine addiction. Only
patients that met the Diagnostic and Statistical Manual of Mental Disorders, third edition
revised (DSM-III-R) criteria for cocaine dependence were included in the study. In order to
isolate cocaine effects from other factors, patients with other addictions, except for tobacco,
and patients with organicity or neurological abnormalities detected on PET scans were
excluded from the study. Brain imaging was done 1 to 6 weeks after the last cocaine use, and
a subgroup of 7 patients underwent a second scan after 3 months of abstinence. A control
group with 18 normal participants paired by sex and age was selected. PET scans were
obtained according to the standardized protocol at resting conditions.
Volkow et al. (1992) reported a reduced metabolism (hypofunctionality) in the prefrontal
cortex (PFC) in cocaine addicts evaluated 1 to 6 weeks after last cocaine use compared with
controls. It is important to note that acute cocaine use induces increased brain activity in
certain areas, especially in the PFC, the same areas that were hypoactive during abstinence.
Hypofunctionality during abstinence suggested neuroadaptive changes induced by the drug in
those areas. Hypofunctionality in the PFC may account for the feelings of anhedonia and
depression, which characterize cocaine withdrawal and often trigger cocaine craving and
relapse. Changes in glucose metabolism include specifically the orbitofrontal and anterior
