Methodological problems in the measurement of drug-induced rotational behaviour: continuous recording reveals time-course differences undetected by previous techniques.

Rats were lesioned unilaterally in the medial forebrain bundle with either the catecholamine neurotoxin 6-hydroxydopamine or the indoleamine neurotoxin 5,6-dihydroxytryptamine. Their rotational responses in automated rotameters to a challenge with the dopamine-receptor agonist apomorphine were compared using four different techniques in current use, and by assessment of complete rotation curves using both conventional statistical procedures and elementary computer-derived elements of curvature. The rotational responses of the two groups, characterized neurochemically by identical depletions of striatal dopamine but with a greater depletion of striatal 5-hydroxytryptamine in 5,6-dihydroxytryptamine-lesioned animals, were indistinguishable using each of the four current techniques. Assessment of rotation curves by both methods revealed significant differences between the two groups, characterised by faster onset and offset of the rotational response in 5,6-dihydroxytryptamine-lesioned animals. Some current techniques may implicitly exclude the detection of such time-course differences in rotational behaviour. Assessment of complete rotation curves may best allow valid comparisons between experimental groups.