Functional interactions of D1 and D3 dopamine receptors, generation and behavioural assessment of mice lacking both receptors

grantor: University of TorontoDopamine is involved in the control of locomotor activity, reward, cognitive and endocrine functions. Experimental evidence suggests that D1 and D3 dopamine receptors interact in an opposing and synergistic fashion. The objective of this project was to generate mice lacking both receptors in order to investigate D1/D3 receptor interactions in behaviour. D1-/-D3 -/- mice were viable, fertile and showed no gross morphological abnormalities. In a novel open field, they exhibited lower activity than wild-type, D1-/-, and D3-/- mice. D1-/-D3-/- mice performed equally poorly in the rotarod and spatial learning tasks as their D1 -/- littermates. Basal locomotor activity and anxiety-like behaviour were normal in D1-/-D3 -/- mice. Combined deletion of both receptors abolished the exploratory hyperactivity and anxiolytic-like behaviour of the D3 receptor mutant phenotype and further attenuated the low exploratory phenotype of D1 -/- mice. These results suggest an interaction of both receptors in the expression of novelty-induced exploratory behaviour and the need for the presence of intact D1 receptor for the expression of certain behaviours manifested by the D3 receptor mutant phenotype. In addition, the D1 receptor, but not the D3 receptor, is involved in the ability to perform on the rotarod as well as spatial learning.M.Sc