Due to the regional expression of D3 dopamine receptors in limbic areas of the brain,
there has been considerable interest in the potential role of this receptor subtype
in mediating emotional behavior. Previous studies in habituated rats have shown that
the putative dopamine D3 receptor antagonist 5,6-dimethoxy-2-(di-n-propylamino)indan
(PNU 99194A) increased locomotor behavior. The present study examined the effects
PNU 99194A on motor and emotional behaviors in C57BL/6J mice. Motor behavior was assessed
in both habituated and nonhabituated mice. Emotional behavior was assessed using the
elevated plus-maze and a social context involving an isolated C57BL/6J mouse and a
nonaggressive conspecific. In mice habituated to the activity chamber prior to drug
administration, PNU 99194A increased locomotion and rearing at lower doses (5, 10
mg/kg) whereas higher doses (20, 30 mg/kg) reduced these behaviors early in the test
session. Thigmotaxis was increased independently of the effects on motor behavior.
In mice exposed to the activity chamber for the first time, PNU 99194A produced a
weak motor activation at lower doses and an initial decrease in motor behavior at
higher doses that was followed by an increase in locomotion later in the test session.
PNU 99194A had no systematic effects on activity in the elevated plus-maze, but dose-dependently
increased flight reactivity in the social reactivity paradigm. These and previous
findings raise questions about the role of dopamine D3 receptors in mediating motor
behavior and emotional reactivity as well as the pharmacology of this putative dopamine
D3 receptor antagonist.