Time sampling observation procedure for studying drug effects: interaction between d-amphetamine and selective dopamine receptor antagonists in the rat.

A rapid time sampling observation procedure combined with two forms of automatic activity assessment is described. The methods are illustrated by examination of the behavioral effects of d-amphetamine, administered to rats either alone or in combination with antagonists selective for D1 or D2 dopamine (DA) receptors. Low doses of d-amphetamine (0.5-4.0 mg/kg) increased photocell counts, rearing, ambulation, and various forms of sniffing. Similar effects were observed in the first 30 min following administration of 8.0 mg/kg d-amphetamine. However, animals exhibited licking, intense sniffing down, and repetitive head and limb movements in the following 30 min; minimal ambulation, rearing, and sniffing up were observed. The "traditional" total photocell count measure did not differentiate between these time-dependent changes in locomotion. On the other hand, latch counts-where subjects had to move between the beams to register a count-adequately demonstrated this change in locomotion. The selective D1 receptor antagonist SCH23390 and selective D2 antagonist raclopride dose dependently inhibited the behavioral changes produced by 1.5 mg/kg d-amphetamine. Higher doses of SCH23390, but not raclopride, produced a behavioral pattern indistinguishable from that observed in control sessions. Both DA antagonists equipotently blocked the intense sniffing down and repetitive head/body movements produced by 8.0 mg/kg d-amphetamine. A narrow intermediate range of doses of SCH23390 reduced the incidences of these behaviors and produced levels of locomotion and sniffing straight that were significantly higher than those observed in control session. This form of behavioral activation was not observed with raclopride. Therefore, this observation procedure revealed subtle differences between the inhibitory effects of SCH23390 and raclopride on d-amphetamine-induced behavioral changes.