Quantitative trait loci contributing to phencyclidine-induced and amphetamine-induced locomotor behavior in inbred...

Phencyclidine (PCP) and amphetamine (AMP) can induce psychotic syndromes in humans, whereas administration of these drugs to mice results in behavioral activation that is influenced by genetic factors. Quantitative trait loci (QTL) underlying genetic differences in response to PCP and AMP in mice were provisionally identified by correlating allelic variation at known marker loci in the BXD series of recombinant inbred (RI) mice and its progenitors (C57BL/6J and DBA/2J inbred strains) with the locomotor response of each strain to PCP and AMP. Total distance traveled for individual mice from each of the 26 BXD RI and two progenitor strains was measured after injections of normal saline and 7.5 mg/kg i.p. injection of PCP. This procedure was repeated after 1 week, using 5.0 mg/kg of AMP, instead of PCP. Markers significantly (p < .01) correlated with response to PCP map to murine chromosomes 1, 14, and 15. Response to amphetamine was correlated with markers mapping to chromosomes 4, 5, 6, 8, 14, and 18. Identification of the QTL underlying PCP-induced and AMP-induced behavior in mice may provide clues into the complicated genetics of psychosis in humans.