Biology Reference
In-Depth Information
after the training period. Intra-VTA, but not intra-SN infusions of BDNF progressively
enhanced cocaine seeking after withdrawal. Cocaine-seeking responses were higher 30 days
after withdrawal than 3 days after withdrawal (Lu et al., 2004). These results suggest that the
increase of BDNF during psychostimulant withdrawal may mediate neuronal plasticity,
leading to synaptic modifications that underlie enhanced responsiveness and compulsive drug
seeking in addicts.
The role of BDNF in synaptic plasticity of the midbrain VTA dopamine neurons during
cocaine withdrawal was further assessed by examining the excitatory properties of the VTA
dopamine neurons. Rodents were treated with cocaine for 5-7 days and then the effectiveness
of the treatment to induce sensitization was assessed through measures of locomotor activity.
Brain slices were obtained sacrificing rodents 10-15 days after last cocaine injection. In VTA
slices, weak presynaptic stimuli, administered on dopamine neurons, evoked persistent
increases in excitatory postsynaptic potentials (EPSPs) amplitude. The enhanced VTA
neuronal responses were found 10-15 days after cocaine withdrawal. However, the
enhancement was not detected 1 day after withdrawal. These results suggest that during
withdrawal VTA dopamine neurons become increasingly excitable and susceptible to the
induction of long-term potentiation (LTP). At the same time, BDNF levels were registered in
the VTA tissues and were also found to have increased after 10-15 days of withdrawal. BDNF
levels in VTA were not detected 1 day after withdrawal. Moreover, when exogenous BDNF
was applied to the VTA, persistent potentiation in dopamine neurons activity was observed
both in naïve rats and after one day of withdrawal. These results suggested that BDNF was
needed for the induction and expression of LTP in VTA synapses (Pu et al., 2006) and
confirmed the role of BDNF, already described as an inductor of LTP and synaptic plasticity
in the hippocampus (Poo et al., 2001).
Taken together, these data suggest that increased BDNF levels in VTA neurons during
withdrawal play a role in synaptic remodeling. Moreover, the results for BDNF confirm the
role of LTP in synaptic plasticity as a basic cellular mechanism underlying information
storage within the neural systems (Geinisman, 2000).
S
YNAPTIC
P
LASTICITY IN THE
S
TRIATUM
The possible use-dependent changes in synaptic efficacy in the striatum, including the
ventral and dorsal striatum, have been widely studied in order to investigate the possible
biochemical and cellular mechanisms that underlie memory and learning and their
implications in human and non-human behavior. In cocaine addiction, it is has been proposed
that strong excitatory synapses on VTA DA neurons will change the level or pattern of DA
release in target structures such as the NAc and modulate DA-dependent learned associations
and behaviors having remarkable consequences on human behavior and emotion (Hyman and
Malenka, 2001; Kalivas and Volkow, 2005). The work in this area has revealed a remarkable
plasticity in striatal cells and their cortical and subcortical projecting structures.
