Tissue level related stereotyped behaviour after intravenous amphetamine in rats

In the first experiment, open field activity was studied in rats after different intravenous doses of d-amphetamine (0.5, 2, 4, 6, 8 mg/kg) at three time points (1-5, 28-32, 58-62 min.). Ambulation and rearing initially increased with increasing amphetamine doses, but at 8 mg/kg the registered activity was replaced by stereotyped disintegrated behaviour. In the second experiment plasma and brain levels of d-amphetamine were determined (at 3, 30 and 60 min.) after 5 different intravenous doses of d-amphetamine (0.25, 0.5, 2, 4, 8 mg/kg). Ambulation and rearing where then plotted against the tissue levels. There was initially a positive correlation between activity and tissue level. At a certain level a maximum was reached, followed by a decline with increasing tissue levels. At 3 min., the decline started after 15 micrograms/g of amphetamine in the brain tissue, at 30 min. this level was 3, and at 60 min. 2 micrograms/g. It is concluded that at least 5 times higher brain concentrations are needed to elicit stereotyped behaviour, than to maintain it later on.