Biology Reference
In-Depth Information
Drugs of abuse also introduce changes in the molecular mechanisms of reward-related
associative learning (Berke and Hyman, 2000) and induce long-term changes in synaptic
effectiveness in critical brain areas (Thomas et al., 2001; Ungless et al., 2001; Saal et al.,
2003, Thomas and Malenka, 2003). In this respect, long-term potentiation (LTP) and long-
term depression (LTD) are forms of synaptic plasticity by which neuronal stimulation induces
changes in synaptic connectivity, making neurons more or less responsive to future activation.
LTP and LTD can lead to changes in synaptic strength that allow modification of the
information flow between different structures of the reward circuitry. This includes, for
example, the information flow coming from the amygdala, hippocampus or PFC to the NAc
and VTA. LTP and LTD as mechanisms of synaptic plasticity may play a critical role in
adaptive associative forms of learning and memory and in pathological processes such as
addiction (Thomas and Malenka, 2003).
Recent evidence suggests that neurotrophins, such as brain-derived neurotrophic factor
(BDNF) and its intracellular signaling pathways, including phosphatidylinositol 3-kinase
(PI3-K) and the mitogen-activated protein kinase (MAPK/ERK) cascades (Heerssen and
Segal, 2002; Kaplan and Miller, 2000; Patapoutian A, Reichardt, 2001), modulate the cellular
mechanism of LTP and memory processes (Mizuno et al., 2003; Rattiner et al., 2005). Recent
evidence suggests that BDNF and its intracellular pathways are part of the molecular
mechanisms that underlie the development of addiction (Grimm et al. 2003; Lu et al., 2004;
Pu et al., 2006).
The brain ability to learn by association has been recognized since the pioneering work of
Ivan Pavlov (1927). Processes such as learning (Stewart and Rusakov, 1995), living in an
either an isolated or complex environment (van Praag et al., 2000) or from recovery from
brain damage (Biernaskie and Corbett, 2001) are forms of experience-dependent learning and
give rise to behavioral changes (Kandel, 1999). These forms of learning represent critical
process through which experiences shape emotion, motivation, behavior and personality
(LeDoux, 2001). There is abundant experimental evidence supporting the idea that synaptic
plasticity may play a role in mediating the behavioral and emotional consequences of
exposure to drugs of abuse and in the development of addiction (Robinson and Berridge,
1993; Kalivas, 1995; Hyman and Malenka, 2001; Nestler, 2001).
The aim of this chapter is to review the mechanisms of synaptic plasticity, including
those involving BDNF, that allow the reorganization of the neural circuits from the first
contact with the drug to the development of the compulsive consumption which characterizes
addiction. Additionally, the diverse neuronal processes that take place in addiction will be put
into context of synaptic plasticity in order to gain a more comprehensive view of the process
of addiction. Studying repeated exposure to cocaine is a useful way of investigating
experience-dependent synaptic plasticity induced in different brain regions as well as its
functional, emotional, and behavioral consequences. The studies of synaptic plasticity related
to cocaine addiction are useful for developing possible therapeutic interventions.
