D-amphetamine, cocaine and caffeine: a comparative study of acute effects on locomotor activity and behavioural...

Although open-field behaviour has been considered a valid and reliable index of locomotor activity in rodents, the simple measures traditionally recorded in this test do not readily allow for differentiation between compounds of the same general class, e.g. psychostimulants. The present methodology was developed to facilitate detailed and continuous observations on the behaviour of drug-treated rats. In addition to an automated (photocell) measure of general locomotor activity, ethological techniques were used to record the frequency and duration of standing, moving, sniffing, rearing, grooming, scratching, sniffing air, freezing, head-swinging and licking. A series of factor analyses was also performed in order to further characterize treatment-induced changes in the structure of behaviour. Compounds studied were d-amphetamine (0.5, 1.5, 3, 6 mg/kg), cocaine (5, 10, 20, 50 mg/kg) and caffeine (5, 10, 20, 40 mg/kg). Although all three psychostimulants increased the automated measure of general locomotor activity, cocaine (which produced the largest effects) monotonically increased general activity over the dose range tested, whereas the stimulant effects of the other two compounds were either reduced (d-amphetamine) or eliminated (caffeine) at higher doses. More detailed observations provided confirmation of the differences in effect produced by these compounds. For example, the frequency and duration of 'moving' dose-dependently increased after cocaine, while d-amphetamine and caffeine again produced bell-shaped dose-response curves. However, whereas low-intermediate doses of d-amphetamine reduced the mean duration of moving, sniffing and rearing, no such effect was observed at the highest dose tested. This finding, together with the appearance of licking in the behavioural repertoire, suggests a stereotyped character to responses seen at high doses of this compound, though neither cocaine nor caffeine induced stereotypy. As factor analyses also revealed quite different behavioural structures associated with these three drugs, present findings demonstrate that detailed observation of behaviour represents a useful approach to research on the behavioural pharmacology of psychostimulants.