Tesis doctoral de Marc Guitart Masip
Hundreds of millions of people experiment with drugs of abuse. Vulnerability to develop addiction has been associated with impulsivity or novelty seeking. The roman rats, genetically selected for high (rha) or low (rla) active avoidance acquisition in the two way shuttle box, appear to be a valid laboratory model of divergent novelty and substance seeking profiles and differ in the functionality of the dopaminergic system. So far, it is known that rha rats drink ethanol voluntarily whereas rla rats do not. In the present thesis, the roman rats have been used as a model of differences in vulnerability to addiction. The aim of the theis was to understand the neurobiological mechanisms that underlie such differences in vulnerability between the two roman rat strains. the work has been divided in 3 experimental blocks. First, we studied the behavioral response to an injection of a low dose of ethanol in these rats. Like those humans at high risk to develop alcoholism, rha rats were less sensitive to the effects of such dose of ethanol. Second, brains of naí¯ve roman rats were studied in order to characterize several molecular targets of the dopaminergic system and related neuropeptides: dopamine receptors subtypes (quantified by means of receptor autoradiography) and mrna coding for neuropeptides (quantified by means of in situ hybridization histochemistry). When compared to rla rats, rha rats showed higher binding of d1 and d3 recptors subtypes and dynorphin mrna expression in the nucleus accumbens shell, although they showed lower d3 basal binding in the calleja islands. Moreover, a challenge with a d3 agonist resulted in greater inhibition of locomotor activity as well as supression of ngfi-a (measured with in situ hybridization) in the calleja magna in rla rats when compared to rha rats. These results provide further evidences of the differences in dopamine function between the roman strains and may represent the neurobiological core of the divergences in novelty
Datos académicos de la tesis doctoral «Divergent sensitivities to drugs of abuse: neurochemical and neuroanatomical characterization of the roman rats.«
- Título de la tesis: Divergent sensitivities to drugs of abuse: neurochemical and neuroanatomical characterization of the roman rats.
- Autor: Marc Guitart Masip
- Universidad: Autónoma de barcelona
- Fecha de lectura de la tesis: 12/12/2006
Dirección y tribunal
- Director de la tesis
- BjÁ¶rn Johansson
- Tribunal
- Presidente del tribunal: miquel Casas brugue
- peter Driscoll (vocal)
- Ortiz de pablo jordi (vocal)
- (vocal)