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Rebecca J. Ralph "Dopaminergic Regulation of Prepulse Inhibition and Locomotor Activity in Mice and Rats: Strain and Species Differences"

Abstract :


P
repulse inhibition of the acoustic startle response (PPI) and locomotor activity have been used to investigate the effects of antipsychotic medications and psychomotor stimulants and the dopaminergic mechanisms underlying the effects of these drugs. Recent studies with inbred mice suggest there may be profound strain and species differences in the dopaminergic modulation of PPI and locomotor activity.
We investigated the D1 and D2 receptor modulation of PPI and locomotor activity in outbred rats (Sprague Dawley) and inbred (129X1/SvJ, C57BL/6J, and DBA/2J) and outbred mice (Swiss Webster). Consistent with previous reports in rats, a D2 agonist was more potent and effective than a D1 agonist for decreasing PPI and increasing motor activity in Sprague Dawley rats. In contrast, the reverse was generally found in mice, suggesting that the D1 receptor has a more prominent role than the D2 receptor in the modulation of these behaviors in several inbred and outbred mouse strains. In ongoing studies, we have examined locomotor activation induced by D1 and D2 agonists in 15 mouse strains.
Consistent with our other results, only a very few mouse strains exhibited increased locomotor activity after administration of the D2 agonist. These findings may aid in the interpretation of results from studies of dopamine-regulated behaviors across rodent species and strains.

Selected publications

Ralph, R.J. and Caine, S.B. (2005). Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: comparison of Sprague Dawley rats to Swiss Webster, 129X1/SvJ, C57BL/6J and DBA/2J mice.
Journal of Pharmacology and Experimental Therapeutics, 312:733-741.
Tsai G., Ralph-Williams, R.J., Martina, M., Bergeron, R., Berger-Sweeney, J., Dunham, K.S., Jiang, Z., Caine, S.B., and Coyle J.T. (2004). Gene knockout of the glycine transporter 1 enhances NMDA receptor responses and spatial memory retention and protects against amphetamine disruption of sensory gating.
Proceedings of the National Academy of Sciences, 101:8485-8490.
Ralph-Williams, R.J., Lehmann-Masten, V., and Geyer, M.A. (2003). Dopamine D1 rather than D2 receptor agonists disrupt prepulse inhibition of startle in mice.
Neuropsychopharmacology. 28:108-118.
Ralph-Williams, R.J., Paulus, M.P., Zhuang, X., Hen, R., and Geyer, M.A. (2003). Valproate attenuates hyperactive and perseverative behaviors in mutant mice with a dysregulated dopamine system.
Biological Psychiatry, 53:352–359.

Françoise Dellu-Hagedorn