A behavioural response, typically in rats or mice, in which the animals turn in head to tail circles. The phenomenon is associated with imbalance in the BASAL GANGLIA, in particular following a unilateral 6-HYDROXYDOPAMINE LESION of the NIGROSTRIATAL DOPAMINE SYSTEM. Although suggested in earlier accounts, the phenomenon and its dependence on central dopamine systems was first clearly described in 1970 by Urban Ungerstedt.
As shown in the figure, unilateral nigrostriatal lesions produce a postural bias towards the side IPSILATERAL to the lesion. However, for rotation to become fully manifest, the animals must be activated either by STRESS, or by a pharmacological agent. AMPHETAMINE induces an increase in dopaminergic activation of the striatum on the CONTRALATERAL side, which is translated functionally into a marked ipsilateral rotation. Conversely, the dopamine receptor agonist APOMORPHINE induces rotation in the contralateral direction, even at very low doses below the threshold for behavioural activation in intact animals. In order to explain these initially unexpected results, Ungerstedt proposed that the dopamine receptors are upregulated as a compensatory response to loss of dopamine inputs. Thus, the hypothesis of receptor SUPERSENSITIVITY was first proposed on the basis of behavioural evidence and has subsequently been confirmed in RECEPTOR BINDING studies.
Rotation is easily automated. In 1970, Ungerstedt & Arbuthnott introduced an apparatus—known as a ROTOMETER—that has been widely adopted. Animals are tested in hemispheric bowls and connected by a harness and tensile wire to a cam-and-pivot switch that transduces turning in quarter, half or full turns in clockwise and anticlockwise directions into incremental counts on an electromechanical or computerized counter. The rate of turning is found to correlate closely with the extent of dopamine loss, so that rotation provides a sensitive and non-invasive behavioural response to monitor the integrity of the underlying nigrostriatal system. As a result of its sensitivity, and the ease of objective and automated recording, rotation has been widely used to evaluate and compare the potency of
The Ungerstedt rotation model.
Notes In the illustration, the left and right NIGROSTRIATAL DOPAMINE SYSTEMS are viewed from above. A LESION (UNILATERAL) made with 6-HYDROXYDOPAMINE (6-OHDA) in the right SUBSTANTIA NIGRA removes DOPAMINE input from the ipsilateral STRIATUM.
A Spontaneous bias to the right. AMPHETAMINE induces dopamine release in the intact striatum (arrow head) and stimulates IPSILATERAL rotation.
B APOMORPHINE acts post-synaptically at RECEPTORS which have developed SUPERSENSITIVITY in the lesioned striatum (arrow head) to induce CONTRALATERAL rotation. (Based on Ungerstedt and Arbuthnott, 1970)
dopamine agonist and stimulant drugs and of novel gene transfer (see GENE TRANSFER IN THE CNS) and TRANSPLANTATION therapies. Although most research has focused on rodents, related results have also been observed in monkeys and humans. For example, patients with PARKINSON’S DISEASE (which is typically asymmetric in its early manifestation), have been fitted with electronic turning sensors, which shows that they make a predominance of turns towards the more affected side in the course of going about their daily activities.
Although the largest body of research has focused on dopaminergic systems and drugs, more modest levels of rotation can be observed following unilateral lesions and pharmacological activation in other neurotransmitter systems, including the SEROTONIN systems associated with the input from the RAPHE NUCLEI and the GLUTAMATE inputs from the CEREBRAL CORTEX to the STRIATUM, CHOLINERGICINTERNEURONS in the striatum and output systems of the basal ganglia (see CORTICOSTRIATAL LOOPS for anatomical detail). A limited degree of rotation can also be revealed in intact animals. Although many animals are asymmetric, others show modest rates of turning in the same direction both spontaneously (when tested overnight to collect enough counts) and following injection of amphetamine. Stanley Glick has shown that these asymmetries correlate with imbalance between the two sides in striatal dopamine concentrations. Larger CONDITIONED ROTATION asymmetries can be induced in intact rats by explicit behavioural conditioning. There are also reports that patients with schizophrenia show spontaneous side biases which can be manifested as rotation.
Rotation must be distinguished from BARREL ROLLING, in which the animals make twisting rolls along a longitudinal body axis, and which is due to damage to the VESTIBULAR COMPLEX.
References
Pycock C.J. (1980) Turning behaviour in animals. Neuroscience 5:461–514.
Ungerstedt U. & Arbuthnott G.W. (1970) Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine le sions of the nigrostriatal dopamine system. Brain Researcb 24:485–493.
STEPHEN B.DUNNETT
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