Research objectives and content
Certain human individuals (sensation seekers) are often involved in both risky activities and psychoactive drug use. A common neurobiological substrate (namely the mesolimbic dopamine system) has been hypothesized to be involved in both novelty seeking and drug use. In the same frame, adolescent human subjects are characterized by elevated levels of sensation seeking, which can perhaps justify the first approaches to recreational drug use. Aim of the present proposal is to specifically investigate this relationship, and to deepen our knowledge on psychobiological risk factors for vulnerability to addiction in an animal model of human adolescence. When compared to adult subjects, periadolescent rats are generally hyperactive, and show both a marked hyporesponsivity to acute psychostimulants effects and peculiar sensitization patterns after repeated drug administration. These age-related differences in response to drugs are suggestive of a differential activation of neural substrates involved in the reinforcing properties of psychostimulants. In animal models of vulnerability to addiction, namely the self-administration paradigm, a relationship between the behavioural and neuroendocrine response to novelty and the effects of psychostimulants has been established. However, these studies have been limited to adult animals. It is proposed the adoption of this kind of analysis in periadolescent rats, in the hypothesis that periadolescent subjects might show an increased vulnerability to drug addiction. The experimental animals are represented by either 60 periadolescent (postnatal days 35-45) or 60 adult S.D. male rats (postnatal days 70-80). Levels of novelty seeking will be assessed, and a fine-grain behavioural analysis will be performed on animals of both ages. All the animals will then be trained and tested daily for AMPH self-administration, for a period of a week. At the end of this paradigm, animals will be sacrificed, and blood and brain removed for determination of plasma ACTH and corticosterone levels, and of monoamine as well as mineral- and gluco-corticoids receptors density and affinity in selected brain areas. Training content (objective, benefit and expected impact) During the requested training, Dr ADRIANI will have the opportunity to share the research experience (i.e. behavioural, pharmacological and
psychoneuroendocrine approach to the study of periadolescent rodents) maturated during the last two years in the Istituto Superiore di Sanita, Roma, Italy. Because of its multidisciplinary approaches, the host research group can provide a very good training in the behavioural assessment of changes in the addictive properties of drugs as well as in the studies of the biological modifications that could underlie such changes. Dr. Adriani will have access to all the necessary equipment for the evaluation of the rewarding properties of drugs in animals, such as intravenous self-administration and place preference cages. The equipment for doing in vivo neurochemical measures of dopaminergic activity such as microdialysis will also be available. The appropriate training to use this material will be provided by experienced members of the research group. This will enhance the scientific skills and expertise of the applicant, and favour the exchange of scientific information.
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