Amphetamine-induced rotational behavior in rats: relationship to hypothalamic and striatal degeneration

When lesions are placed unilaterally in the nigrostriatal system of experimental animals, rotational behavior occurs in response to peripheral administration of dopamine (DA) agonists. In spite of considerable evidence to the contrary, it is assumed that in order for this rotation to occur, an almost complete depletion of striatal DA must be achieved. To test this hypothesis further, 20 male Sprague-Dawley rats were injected unilaterally with 2 microL of 8 micrograms/microL of 6-hydroxydopamine (6-OHDA) via acute injection needles or chronically indwelling cannulae. Acute injection of 6-OHDA resulted in a rotation rate of 7.2 to 18.9 revolutions per minute in response to peripheral amphetamine injection (5 mg/Kg) while injection of 6-OHDA through chronically indwelling cannulae produced rotation ranging from 1.4 to 9.9 rotations per minute. Under the conditions of either method of injection, the animals displaying the most severe rotation still showed partial denervation of striatal DA as revealed by catecholamine fluorescence histochemistry. Conversely, numerous animals demonstrating very low rates of amphetamine-induced rotation often displayed a complete loss of striatal, accumbens, and olfactory tubercle catecholamine fluorescence. Moreover, large quantities of lateral hypothalamic amine accumulation were observed in rotating rats indicating that this neurochemical change may be of functional significance for rotational responses. The present results, when taken into consideration with previous work, indicate that the routine selection of rotating animals for pharmacological testing for potential antiParkinsonian medication or intracerebral grafting purely on the basis of their rotational behavior does not necessarily imply that complete striatal denervation has occurred. Moreover, these findings demonstrate that amine accumulation in the lateral hypothalamus of rotating animals with DA depleting lesions is an important phenomenon implicated in the expression of rotational behavior in animals and possibly in the pathophysiology of Parkinson's disease.