Neuroimaging

Section Head

Research Objective

The neurochemical basis of neuropsychiatric illness and mechanisms of drug actions are investigated, using animal models and brain imaging techniques, to advance basic and applied knowledge of mental illnesses and addictive behaviours.

Summary of Activities

Research in the Neuroimaging Section is aimed at mapping changes in specific brain areas, neuroanatomical pathways and chemical mechanisms in neuropsychiatric disorders primarily through detailed analyses in anatomically preserved brains from animals.

Models of depression and stress reactions

The learned helplessness model of depression continues to be used to test animals showing a propensity to develop depressive-type symptoms in response to stress. Significant changes in gene expression have been identified in the forebrain of stress-susceptible and stress-resistant animals.

In the context of stress reactions, scientists continue to study sleep deprivation, to identify possible mechanisms involved in its beneficial (antidepressant) effects as well as its potentially harmful effects. Collaboration with scientists at the Federal University of São Paulo, Brazil has led to the identification of changes in the brain expression of specific subtypes of thyroid hormone receptors in the chronic mild stress model of depression, suggesting a potential involvement of these receptors in antidepressant effects.

Models of antipsychotic drug action

In a major collaborative effort with CAMH colleagues aimed at understanding brain mechanisms underlying differences between newer and older types of antipsychotic drugs, scientists are studying early gene (c-fos) activation induced by several drugs in conjunction with receptor occupancy and behavioural measures. Long-term motor side-effects induced by long-term treatment with classic antipsychotic medications are an important clinical problem. Using the vacuous chewing movement (VCM) model of tardive dyskinetic syndromes, scientists have found that the emergence of motor side-effects may depend crucially on the regimen of drug administration and may be reversed by targeting specific serotonin or adenosine receptors. Brain changes occurring in another chronic movement disorder model, the dtsz mutant hamster, are also mapped using brain imaging techniques. This work is being carried out in collaboration Dr. A. Richter in Berlin, Germany.

Brain mechanisms of compulsive drug-taking

Repeated exposure to drugs of abuse results in an increased sensitivity to their behavioral effects. Brain mechanisms underlying differential susceptibility to behavioural sensitization to alcohol continue to be an important focus of research. Work with dopamine receptor knockout (KO) mice, which lack specific types of dopamine receptors by inactivating or "knocking out" the genes for the receptors in mouse embryos, indicates that D₁ and D₃ receptors, but not D₂ receptors may be critical for behavioural sensitization to ethanol.