Modification of dopamine D1 receptor knockout phenotype in mice lacking both dopamine D1 and D3 receptors

Experimental evidence suggests that dopamine D-1 and D-3 receptors may interact in an opposing or synergistic fashion. To investigate interactions between both receptors in behaviour, we have used dopamine D-1 and D-3 receptor knockout mice to generate mice lacking both receptors. D1-/-D3-/- mice were viable, fertile and showed no gross morphological abnormalities. In an open field, they exhibited lower activity than wild-type, D-1(-/-) and D-3(-/-) mice. D1-/-D3-/- mice performed equally poorly in the rotarod and Morris water maze tasks as their D-1(-/-) 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 dopamine D-3 receptor mutant phenotype and further attenuated the low exploratory phenotype of D-1(-/-) mice. These results imply an interaction of both receptors in the expression of exploratory behaviour in a novel environment, and the need for the presence of intact dopamine D-1 receptor for the expression of certain behaviours manifested in dopamine D-3 receptor mutant phenotype. In addition, dopamine D-1 receptor, but not dopamine D-3 receptor, is involved in the ability to perform on the rotarod and spatial learning. (C) 2000 Elsevier Science B.V. All rights reserved.