EFFECTS OF REPEATED AMPHETAMINE TREATMENT ON THE LOCOMOTOR-ACTIVITY OF THE DOPAMINE D-1A-DEFICIENT MOUSE

THE role of dopamine D-1A receptors in mediating amphetamine-induced s ensitization was investigated using the D-1A-deficient mouse. During t he drug preexposure phase, D-1A-deficient and control mice were inject ed for five consecutive days with saline or amphetamine (2 mg/kg, i.p. ). Locomotor activity was measured on the first and fifth pre-exposure day. After three abstinence days, mice were given either amphetamine or saline and locomotor activity was again assessed. Mice were then sa crificed and protein kinase A (PKA) activity was measured. In contrast to control mice, D-1A-deficient mice did not show a progressive incre ase in locomotor activity across days. Importantly, both control and m utant mice did exhibit behavioral sensitization, because mice pre-expo sed and tested with amphetamine were more active than mice acutely tes ted with the drug. Even so, the amphetamine-induced locomotor activity of the mutant mice was significantly reduced when compared with simil arly treated control mice, indicating that the sensitized response was less pronounced in the D-1A-deficient mouse. PKA activity also varied depending on genotype, since amphetamine decreased PKA activity in co ntrol but not D-1A-deficient mice.