Effects of repeated administration of methamphetamine on P3-like potentials in rats

Effects of repeated administration of methamphetamine (MAP) on a component of the cortical event-related potential (ERP), P3-like potential which corresponds to the human P3b, were examined in rats performing an active discrimination task. Rats were trained to press a bar within 1200 ms after cessation of a target tone (1000 Hz) lasting for 800 ms, and to withhold an overt response to the standard tone (2000 Hz). The rats were given intracranial electrical stimulation to the medial forebrain bundle as a reward, only when they correctly responded to the target tone. ERPs before drug administration were recorded after the correct response ratio exceeded 85%. Thereafter, a daily dose of 4 mg/kg of MAP, or the same volume of saline in another group, was administered intraperitoneally 15 times. ERPs were recorded again 7-10 days after the last injection. In the rats which received MAP the amplitude of the P3-like potential decreased with no change in its latency, while the response latency of bar-pressing and the correct response ratio were not altered significantly. These results suggest some changes in catecholaminergic transmission induced by repeated MAP-administration affect a P3 generation mechanism. MAP-treated rats may be useful as an animal model to investigate neural mechanisms of MAP-psychosis and schizophrenia.