In the adult mouse, single and compound null mutations in the genes fo
r retinoic acid receptor beta and retinoid X receptors beta and gamma
resulted in locomotor defects related to dysfunction of the mesolimbic
dopamine signaling pathway. Expression of the D1 and D2 receptors for
dopamine was reduced in the ventral striatum of mutant mice, and the
response of double null mutant mice to cocaine, which affects dopamine
signaling in the mesolimbic system, was blunted. Thus, retinoid recep
tors are involved in the regulation of brain functions, and retinoic a
cid signaling defects may contribute to pathologies such as Parkinson'
s disease and schizophrenia.