RESUMO
To determine whether noradrenaline (NA) is an essential neurotransmitter for addictive and appetitive behaviors, we measured drug and food seeking in transgenic mice lacking dopamine beta-hydroxylase (Dbh), the enzyme responsible for synthesizing NA. Using the conditioned place preference test (CPP), we show that Dbh -/- mice do not exhibit rewarding behavior to morphine, cocaine, or the mixed reuptake inhibitor bupropion. In spite of their lack of preference for drugs, Dbh -/- mice had an unaltered preference for food. Drug seeking was induced when NA was restored to the central nervous system of Dbh -/- mice by administration of l-threo-3,4-dihydroxyphenylserine (DOPS) and carbidopa. When a NK1 receptor antagonist was co-administered with morphine or cocaine, it produced aversive behavior in Dbh -/- mice while it abolished place preference in the controls. NK1 antagonists alone did not have any rewarding or aversive effect in the CPP suggesting that substance P opposes some of the unpleasant effects of morphine and cocaine. Our results show that NAergic transmission is necessary for motivated behaviors, the dysregulation of which is a co-morbid factor of many depressive states. The reversibility of this phenomenon, by restoring NA, indicates that even when this behavioral deficit is genetically determined it can be reversed.