Biology Reference
In-Depth Information
Figure 1. BDNF and the ERK intracellular signaling pathway. This figure depicts the ERK BDNF
signaling cascade involved in cocaine addiction and its interaction with dopamine and glutamate
intracellular messengers. There is a cross-talk between the BDNF intracellular signaling mechanism
and those of the glutamate and dopamine transmission. (Source: Adapted from Corominas et al., 2007).
LTP
A
ND
LTD
C
AN
B
E
I
NDUCED IN THE
D
OPAMINERGIC
S
YSTEM
AFTER
C
OCAINE
T
REATMENT
It is well accepted that dopaminergic circuitry, including midbrain dopamine cells, limbic
nuclei including NAc, dorsal striatum, amygdala and hippocampus, and the PFC can undergo
LTP and LTD. These cellular mechanisms involve changes in glutamate transmission and its
receptors, but in the structures related with drug consumption the dopaminergic system is also
involved (Calabresi et al., 1992; Centonze et al., 1999; Goto and Grace, 2005a).
To generate LTP in the lab several models have been used, some of them in vitro after the
animal is sacrificed and others in vivo. The latter have the advantage of maintaining
physiological conditions and patterns of neurotransmitter release, although it requires
stereotaxis procedures to locate target areas to be examined. For example in a standard
procedure, Sprague Dawley rats (between 14 and 42 days) were previously anesthetized and
then sacrificed. Then, the brain is extracted and the block of tissue containing the midbrain
VTA was sliced and prepared for cell-recording by means of electrodes (see figure 2). In a
typical experiment, the effectiveness of the synapses between cells was monitored by giving a
brief electrical stimulus to a bundle of presynaptic axons (afferents from the prefrontal cortex
to the VTA). The electrical stimulation necessary to induce LTP is a brief burst of high-
frequency electrical stimulation, typically 50-100 stimuli at a rate of 100/sec (“tetanus” or
tetanic stimulation). At the same time, it is necessary to induce postsynaptic depolarization (to
