Inhibition of methylphenidate-induced behaviors in rats: differences among neuroleptics.

Methylphenidate (MPD) increased in rats the incidence of sniffing, rearing and locomotion, and this along dose-response curves that had an inverted U-shape; at 40 mg/kg, MPD exclusively induced stereotyped gnawing, which was inhibited by neuroleptics. However, as gnawing induced by 40 mg/kg MPD was inhibited in a dose-dependent manner, other responses (i.e., sniffing, rearing and locomotion) appeared. Higher doses of neuroleptics also inhibited these latter responses, so that the behavior of the MPD-treated animals became similar to that of normal controls. Only some nonsedative neuroleptics appeared able to normalize the behavior of MPD-treated rats at doses that induced neither complete behavioral suppression nor adverse effects. The neuroleptics differed markedly, however, in terms of the relative doses at which they 1) inhibited gnawing, 2) inhibited the other effects of MPD and 3) induced complete behavioral suppression and/or adverse effects. This variation among neuroleptics, which appears to represent a novel aspect of their ability to antagonize behavioral effects of central nervous system stimulants, may be based on differences in the extent to which they exert agonist activity at dopamine receptors. Assuming that MPD-induced behaviors model the positive symptoms of schizophrenia, it may be hypothesized that the differences among the neuroleptics observed here provide an indication of their efficacy to reduce positive symptoms in schizophrenics.