BEHAVIORAL-EFFECTS OF PERSISTENT LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INFECTION IN MICE

Lymphocytic choriomeningitis virus (LCMV) is a nonlytic murine virus t hat provides a valuable model system for studying the behavioral corre lates of CNS viral infection. Newborn or immunosuppressed mice infecte d with LCMV develop a persistent tolerant infection characterized by c ontinuous viral production. Virus can be found in various body organs including lung, liver, kidney, and brain. In brain, neurons are the pr edominant CNS cells infected and the greatest number of persistently i nfected neurons are found in the cerebral cortex, hippocampus, other l imbic structures and parts of the hypothalamus. Despite continuous inf ection throughout the animal's life, neurons show no structural injury or dropout. Mice from the DBA/2J strain were infected with LCMV (1000 plaque-forming units) within 18 h of birth and tested for behavioral function as adults. Plaque assays indicated persistent infection in vi rus-injected mice. Mice were tested for their ability to learn a Y-maz e spatial discrimination to avoid the onset of a mild footshock (0.43 mA). The number of correct avoidance responses made during training wa s taken as a measure of acquisition performance. The virus-infected mi ce showed a deficit in acquisition of the Y-maze discrimination compar ed to that seen in vehicle-injected and noninjected controls. Followin g additional training to reach control levels of performance, the infe cted mice and the controls were injected with the cholinergic antagoni st scopolamine. Scopolamine (2.0 mg/kg) disrupted the performance of t he infected mice significantly more than control performance, suggesti ng that a cholinergic dysfunction accounted for some of the learning d eficit. A separate group of virus-infected mice exhibited hypoactivity during the first exposure to a locomotor testing apparatus. Scopolami ne (2.0 mg/kg) produced locomotor hyperactivity in all three groups co mpared to saline, whereas a lower scopolamine dose, 0.3 mg/kg, produce d hyperactivity selectively in the virus infected mice. Overall, our r esults indicate that LCMV infection causes pronounced behavioral effec ts and an increased sensitivity to cholinergic antagonists. (C) 1994 A cademic Press, Inc.