Organic cation transporters (OCTs) are carrier-type permeases known to 
participate in general detoxification functions in peripheral tissues. Previous 
in vitro studies have suggested that OCTs ensure Uptake2, a low-affinity, 
corticosteroid-sensitive catecholamine removal system, which was characterized 
initially in sympathetically innervated tissues. Although the presence of both 
Uptake(2)-like transport and most OCT subtypes has also been demonstrated in the 
brain, the physiological role of this family of transporters in CNS remained 
totally unknown. In the present work, we show that the OCT3 transporter is found 
throughout the brain and highly expressed in regions regulating fluid exchange, 
including circumventricular organs such as area postrema and subfornical organ 
(SFO), and in other structures implicated in the sensing of changes in blood 
osmolarity and regulation of salt and water ingestion. OCT3/Slc22a3-deficient 
mice show an increase in the level of ingestion of hypertonic saline under 
thirst and salt appetite conditions, as well as alterations of the neural 
response in the SFO after sodium deprivation, as monitored by Fos 
immunoreactivity. This work demonstrates that the presence of OCT3 is critical 
for the balanced neural and behavioral responses to environmentally induced 
variations in osmolarity and provides for the first time physiological evidence 
of the importance of OCTs for CNS function.