Stress alters caffeine action on investigatory behaviour and behavioural inhibition in the mouse

A lot of studies have demonstrated that the physiological action of drugs can be modified by stressors. The present study investigates the effects of stressors on caffeine action on investigatory behaviour and behavioural inhibition in C57Bl6/J mice. For 6 consecutive days, the mice were subjected to one stressful procedure each day consisting on days 1 and 3 of immersion in cold water for 10 periods of 10s each, on days 2 and 5 of a restraint stress for 2 periods of 5 min each, and on days 3 and 6 of placing the animals in a lit openfield for a 10-min period. Saline or caffeine (30, 60 or 120 mgkg-1) were i.p. administered immediately after the last stressful experience, and the animals were tested behaviourally 10 min later. Their behaviour was compared to that of unstressed mice injected with either saline or caffeine. The results show that: (1) in saline-treated mice, stress decreased the investigatory behaviour and increased the behavioural inhibition; (2) in unstressed mice, caffeine decreased the investigatory behaviour in a dose-dependent manner; moreover, behavioural disinhibition, which appeared at low doses of the drug, did not at higher doses; (3) in stressed mice, the dose-dependent action of caffeine was almost abolished and the drug elicited, whatever the dose, a slight increase of the investigatory behaviour and a strong behavioural disinhibition. It is concluded that stress antagonizes the inhibitory action of caffeine on the investigatory behaviour and potentiates its action on behavioural disinhibition. The results are discussed in terms of interaction of stress and caffeine on the dopaminergic system.