Grant: Operating Grant

Emotional processes and higher-order executive functions are governed in part by interconnected neural networks linking the amygdala (a brain nucleus in the temporal lobes) and dopamine input arising from the from the midbrain, to the frontal lobes. Drug addicts, particularly those abusing psychostimulants such as amphetamine or cocaine, display impairments in cognitive functions mediated by these neural circuits. In addition, recent experimental evidence suggests that the brain regions comprising this circuit may be particularly susceptible to long-term neurochemical, anatomical and neurophysiological alterations following repeated exposure to these drugs of abuse. The main objective of the present proposal is to elucidate the neuroadaptations that occur in these circuits following repeated exposure to psychostimulants. We will use amphetamine-induced behavioural sensitization as an animal model of the neural changes that occur following repeated drug exposure, in combination with multidisciplinary analyses combining electrophysiological and behavioural measures that are a hallmark of our research program. Specifically, we will characterize how repeated amphetamine exposure i) disrupts reward-related learning for natural reinforcers such as food, ii) may affect behaviour guided by conditioned aversive stimuli and iii) perturbs in the neurophysiological properties of amygdala neurons and how the actions of dopamine on these cells are altered. Using animal models to investigate the changes that chronic drugs of abuse can induces in these circuits will provide important insight into the aberrant brain function that underlies drug addiction, and may in turn facilitate the development of treatments for the cognitive dysfunction that occurs in this disease.