The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

Pramipexole (PRA) is a preferential D3R agonist that, in rats and humans, modifies prepulse inhibition (PPI) of the acoustic startle reflex, an operational measure of sensorimotor gating. The ability to use similar PPI measures across species, and the relative ease of genetic manipulations in mice, suggests that molecular studies of the D3R regulation of sensorimotor gating might be best pursued in mice. Here, we evaluate the effects of PRA on PPI and locomotion in C57BL/6J mice, the background strain for many gene knockout mouse models. Male C57BL/6J mice were tested for PPI and locomotor activity after injection of PRA. No significant effects of PRA on PPI were observed at any dose (0.1-10.0 mg/kg), but a significant reduction in startle magnitude was observed after 10 mg/kg PRA. In contrast, the D1/2 agonist, apomorphine (5 mg/kg) significantly reduced PPI in these mice. At doses of PRA that did not alter startle magnitude (0.3, 1, 3 mg/kg), significant decreases in the amount of locomotor and investigatory behavior were observed. Distinct from findings in rats and humans, it seems that either: (i) PRA does not activate D3Rs in C57BL/6J mice, or (ii) D3R agonists are not sufficient to alter PPI in this mouse strain. Behavioural Pharmacology 21:135-143 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.