STUDIES ON DRUG-INDUCED STEREOTYPED BEHAVIORS IN THE RAT

Abstract

Methamphetamine (MAP), ephedrine (EPH) and cocaine (COC) are frequently abused and sometimes result in psychotoxic effects in human. The present study was undertaken to examine the effects of single and repeated administration of MAP (1.25-10mg/kg s.c.), EPH (20-80mg/kg i.p.) and COC (10-40mg/kg i.p.) on stereotyped behavior, such as sniffing (SN), head-bobbing (HB), licking (LI), head-weaving (HW), turning (TU), back-pedalling (BP) and gnawing (GN) in rats, as animal models of psychotoxic symptoms. Moreover, in order to investigate the neurochemical basis for such changes, the brain levels of dopamine, noradrenaline and their metabolites were determined in the striatum.
Among these drugs, MAP produced the most dynamic and diverse behavioral changes in the following order : locomotion-and rearing-increase→SN→HB→LI and HW→TU, BP and GN. The behavioral effects of EPH resembled those of MAP, though the activities v, ere low. However, COC failed to produce LI, HW, TU, BP or GN even in the subconvulsive dose of 40mg/kg i.p. Of these stereotyped behaviors, SN and HB were found to be strongly dose-dependent in all cases of administration of the three drugs. When the drugs were repeatedly administered, the SN-and HB-producing effects markedly enhanced showing the reverse tolerance, but no reverse tolerance to the other stereotypy-producing effects. Once reverse tolerance was established, it was maintained for 1 month after the drug was discontinued.
The neurochemical studies demonstrated that dopaminergic neurons play an important role in the development of reverse tolerance to the SN-and HB-producing effects in all cases in which the three drugs were administered. It was also suggested that noradrenergic neurons are involved in the case of COC administration.