Increased discriminative stimulus potency of phencyclidine in C57Bl/6 miceinfected with the LP-BM5 retrovirus

Drug discrimination procedures in mice are used to study the neuropharmacol ogy of a wide variety of drugs. In C57 B1/6 mice, infection with the LP-BM5 murine leukemia virus leads to a syndrome (murine acquired immunodeficienc y syndrome-MAIDS) characterized by immunocompromise, neurochemical alterati ons, and learning and memory deficits. Because the neurochemical and behavi oral changes suggest that altered glutamatergic neurotransmission follows L P-BM5 infection, we studied the effects of infection on discriminative stim ulus properties of phencyclidine (PCP), a Ca2+ channel blocker at NMDA rece ptors. We also tested D-amphetamine and dizocilpine to assess the specifici ty of the discrimination. As expected, dizocilpine produced PCP-like respon ding. After animals were trained to discriminate PCP from saline, they were inoculated with LP-BM5 and the PCP dose-response functions repeatedly dete rmined. The potency of PCP in this procedure was unchanged 3 weeks after in fection, but was increased approximately fivefold 6 and 9 weeks after infec tion. Amphetamine 9 weeks after inoculation did not produce PCP-like respon ding, showing that the results were not caused by a loss of specificity of the discrimination. The time course for changes in PCP potency is similar t o those of other behavioral and neurochemical changes reported after LP-BM5 infection. The results are consistent with an action of LP-BM5 infection a t glutamatergic synapses. (C) 1999 Elsevier Science B.V. All rights reserve d.