Phencyclidine-induced impairment in attention and response control depends on the background genotype of mice: Reversal by the mGLU2/3 receptor agonist LY379268

Rationale: Converging evidence implicates glutamate neurotransmission in attention and inhibitory response control. Objective: To investigate how the background genotype contributes to glutamate's effects on attention and response control, we examined how phencyclidine (PCP) affected the performance of a five-choice serial reaction time (5-CSRT) task in two inbred mouse strains, C57BL/6N and DBA/2N. We also tested a potent mGlu_2/3 receptor agonist, LY379268, against PCP's effects. Methods: Mice were trained on a 5-CSRT task, which measures visual attention and response control until they reached asymptotic performance. Both strains of mice were then injected intraperitoneally with 0.5, 1.5 or 3.0 mg/kg PCP. Doses of 1.0 and 3.0 mg/kg of LY379268 were injected subcutaneously to vehicle or PCP-treated mice. Results: At asymptotic performance DBA/2N mice were less accurate and made more anticipatory responses than C57BL/6N. PCP impaired accuracy (% correct) and increased perseverative responses of DBA/2N mice at 1.5 mg/kg. However, at doses up to 3.0 mg/kg it had no effect on these measures in C57BL/6N. In DBA/2N mice 1.5 mg/kg PCP increased anticipatory responses far more than 3.0 mg/kg in C57BL/6N mice. No dose of LY379268 prevented the PCP-induced accuracy deficit of DBA/2N mice. The PCP-induced anticipatory and perseverative responding of DBA/2N mice was reduced by 3.0 mg/kg LY379268, while 1.0 and 3.0 mg/kg reduced anticipatory responding in C57BL/6N. Conclusions: The background genotype may determine the effects of PCP on attentional performance and the results confirm the importance of glutamate transmission in some aspects of this performance.