Avaliação da influência do estresse e estímulos contextuais no desenvolvimento da dependência : abordagem comportamental e molecular
Abstract
This thesis is part of the requirements for obtaining Ph.D. title by Joint
Graduate Program in Physiological Sciences, UFSCar/UNESP.
The results presented refer to experiments developed in Laboratório de
Neuropsicofarmacologia da Faculdade de Ciências Farmacêuticas de
Araraquara and Behavioral Neurosciense Branch / National Institute on Drug
Abuse - National Institutes of Health, Baltimore, USA.
In chapter 1 we made a general introduction on the theories that
formed the basis of the current concept of drug addiction. In this chapter, we
elaborate a brief history of social organization and human relationship with
drugs. We wrote specifically about both substances used in our studies, ethanol
and cocaine, as well as their impact on public health and the pharmacological
mechanisms of action.
In chapter 2 the aim was to evaluate the influence of factors such as
early age of onset of ethanol use and the effect of stress on the seeking
behavior and consumption of this drug. For this, we used the animal model of
ethanol self-administration and two types of social stress (social deprivation and
social instability) in rats during adolescence. To verify whether behavioral
changes were promoted by molecular neuroadaptations, we quantified gene
expression involved in the development of ethanol dependence in amygdala,
responsible area for stress-induce behaviors.
In chapter 3 we investigated whether daun02 inactivation method is
able to inhibit cocaine-induced locomotor sensitization in rats. This method is
based on the theory that only a small group of sparsely distributed neurons
(neuronal ensembles) are activated during behavior exhibition. For this purpose,
we used transgenic rats carrying a c-fos-lacZ promoter which when activated
induces the expression of ß-galactosidase enzyme only in activated neurons.
The ß-galactosidase converts the prodrug daun02 into a toxic metabolite,
driving to cell apoptosis. Thus, we evaluated whether the neuronal ensembles
activated during the development of locomotor sensitization are the same as
those recruited in the expression of this behavior.
In chapter 4 we investigate whether mice express context-specific
locomotor sensitization and whether the exhibiton of this behavior is related to
synaptic changes in the nucleus accumbens. For this we use male and female
transgenic C57BL/6 adult mice expressing Fos-GFP, a protein sensitive to
green light, only in activated cells. Thus, using a confocal microscope, we
assessed the presence of silent synapses only in activated neurons (neuronal
ensembles) related to the expression of locomotor sensitization.
Like us, researchers in the field of neurobiology of drug addiction have
been studying the factors that can facilitate the initiation and maintenance of
drug use and how it may trigger the addiction. Thus, this thesis aimed to
investigate the influence of age, sex, stress, memory, associative learning,
different types of drugs (cocaine and ethanol) and different types of animal
models (self-administration and sensitization) in the development of drug
addiction.