Persistence of Dose Related Behaviour in Mice

Abstract

IF naive rats are injected with an amphetamine–barbiturate mixture similar to ‘Drinamyl’ and are tested in an unfamiliar environment—a Y-shaped runway—their spontaneous activity is about double that of controls given only saline¹. If, after testing, the rats are returned to their home cages and retested in the runway without drugs, about half of the stimulant effect of the drug mixture can still be detected as much as 3 months later^2,3. This is surprising, for significant amounts of the individual drugs or of any known metabolites are unlikely to be present in the animals' brains for longer than at most 48 h^4,5, though as far as we know information of this kind is not available for mixtures of the drugs. In any case, no such behavioural after-effects can be detected after one or a series of “passive” administrations of the drugs, whereby the rats are merely injected and replaced in the home cage without being tested³ (R. D. Porsolt, unpublished results and refs. 6 and 7). Only when drug administration is combined with an actual test experience do these long term after-effects seem to occur. In the conditions described they are consistent and reliable and are presumably due to some more or less permanent changes in the organism, which are induced by the first drug/environment experience and which affect subsequent behaviour.