Biology Reference
In-Depth Information
providing a mechanism for dampening critical cortical signals (Bamford et al., 2004). Tang et
al., (2001) suggest that the major role for DA and D2 receptors in striatum is to limit the
efficacy of striatal glutamatergic synaptic inputs to MSN.
The dopaminergic lose in the striatal spiny neurons is followed by a cascade of events
that ultimately changes its structure and the activity of basal ganglia circuits, resulting in the
development of PD symptomatology. The specific mechanisms leading to the spiny neurons
morphological changes are not well understood, but may involve glutamate hyperactivity
(Ingham et al., 1998).
The etiology of PD is still not fully understood, but animal models, human post-mortem
material and genetic analyses have provided important clues.
Chemical neurotoxins have been widely used in creating several animal models of human
neurodegenerative diseases in order to assess the neurochemical, physiological and behavioral
effects of lesioning specific neuronal populations. The catecholamine-specific neurotoxin 6-
hydroxydopamine (6-OHDA) has been widely used to destroy dopamine-containing cells in
the SNc and produces an animal model of PD (Dauer and Przedborski, 2003; Schober, 2004).
In recent years attention has been focused on perforated synapses considering their
possible involvement in synaptic plasticity in the nervous system. It has been hypothesized
that an increase in the number of synapses may represent a structural basis for the enduring
expression of synaptic plasticity during some events that involve memory and learning; also it
has been suggested that perforated synapses increase in number after some experimental
situations. Thus the aim of this study was to analyze whether the DA depletion produces
changes in the synaptology of the corpus striatum of rats after the unilateral injection of 6-
OHDA.
M
ETHODS
The experiments were carried out in 70 male Wistar rats weighing 190 ± 10 g at the
beginning of the study. The animals were housed in a controlled environment with a 12-h
light/dark cycle and free access to food pellets and water.
Surgical and Drug Treatment Procedures
The rats were anesthetized with sodium pentobarbitone (35 mg/Kg i.p.) and placed in a
stereotaxic apparatus. The rats were injected with 4 μl of a saline solution containing 8 μg of
6-OHDA (Sigma Chemical, Co.) (n = 35) and 0.2 mg of ascorbic acid into the right medial
forebrain bundle and sham lesion was made with the vehicle (n = 35). The injections were
given over a 4-min period with a Hamilton syringe attached to a glass micropipette with a tip
diameter of 20-50 μm. The stereotaxic coordinates were as follows: AP = -4mm anterior of
the ear bar; L = 1.4 mm lateral of bregma; V = -7.7 mm vertical of dura (according to
Paxinos & Watson, 1986). After recovery from the anaesthesia the animals were returned to
their home cages with free access to food and water, in a cyclical 12-h light-dark
environment.
