QUANTITATIVE TRAIT LOCI CONTRIBUTING TO PHENCYCLIDINE-INDUCED AND AMPHETAMINE-INDUCED LOCOMOTOR BEHAVIOR IN INBRED MICE

Phencyclidine (PCP) and amphetamine (AMP) can induce psychotic syndrom es in humans, whereas administration of these drugs to mice results in behavioral activation that is influenced by genetic factors. Quantita tive trait loci (QTL) underlying genetic differences in responses to P CP and AMP in mice were provisionally identified by correlating alleli c variation at known marker loci in the BXD series of recombinant inbr ed (RI) mice and its progenitors (C57BL/6J and DBA/2J inbred strains) with the locomotor response of each strain to PCP and AMP. Total dista nce traveled for individual mice from each of the 26 BXD RI and two pr ogenitor strains was measured after injections of normal saline and 7. 5 mg/kg IP injection of PCP. This procedure was repeated after 1 week, using 5.0 mg/kg of AMP, instead of PCP. Markers significantly (p < .0 1) correlated with response to PCP map to murine chromosomes 1, 14, an d 15. Response to amphetamine was correlated with markers mapping to c hromosomes 4, 5, 6, 8, 14, and 18. Identification of the QTL underlyin g PCP-induced and AMP-induced behavior in mice may provide clues into the complicated genetics of psychosis in humans. (C) 1996 American Col lege of Neuropsychopharmacology