Head-turning induced by electrical stimulation of the caudate nucleus and its antagonism by anti-parkinson drugs.
Intermittent high-frequency electrical stimulation of the caudate nucleus induces contralateralhead-turning in rats. The anti-Parkinson drugs, L-dopa, amantadine and apomorphine, raise the threshold for or completely inhibit head-turning. There was a high correlation between the predicted clinical potency and these drugs based on inhibition of head-turning and their respective clinical anti-Parkinson potency. The centrally acting anticholinergic drugs also antagonized head-turning but there was not a good correlation between the predicted and acutal anti-Parkinson doses used in man. In order to determine if these drugs blocked head-turning by acting on the caudate nucleus, a combination cannula and stimulating electrode was used to administer drugs directly into the same area of the caudate nucleus being stimulated electrically. Dopamine, amantadine and apomorphine each antagonized head-turning when infused into the same site, at doses which did not produce concurrent overt sterotyped behavior. Time- and dose-response data with all three drugs suggest a direct inhibitory action on the caudate nucleus consistent with their proposed mechanism for treatment of Parkinson symptomatology. Head-turning appears to be a useful animal model for the development of new, specific anti-Parkinson drugs and for the study of possible mechanism(s) of action of existing drugs.
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001590:Benztropine / Q000494:pharmacology; D002421:Caudate Nucleus / Q000502:physiology*; D003864:Depression, Chemical; D004558:Electric Stimulation; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects; D014282:Trihexyphenidyl / Q000494:pharmacology
D000978:Antiparkinson Agents; D001590:Benztropine; D007980:Levodopa; D014282:Trihexyphenidyl; D000547:Amantadine; D001058:Apomorphine