Diminished amphetamine anorexia and enhanced fenfluramine anorexia after midbrain 6-hydroxydopamine.
Rats were made hyperphagic by 6-hydroxydopamine (6-OHDA) injected bilaterally into the ventral midbrain; then they were restricted to a 6 h/day feeding schedule and tested for appetite suppression with amphetamine and fenfluramine in randomized order. Amphetamine anorexia was diminished while fenfluramine anorexia was enhanced (both P less than 0.001). The opposite effect on fenfluramine anorexia shows that the effect of 6-OHDA on amphetamine anorexia was not due to hyperphagia masking the anorexia. Norepinephrine in the forebrain was 90% depleted, but DA and serotonin levels were within 9% of normal. These results demonstrate a new way to dissociate amphetamine and fenfluramine anorexia, as others have done with lateral hypothalamic lesions or DA depletion. The 6-OHDA injections, which were of a type that cause hyperphagia, apparently destroyed a substrate for amphetamine anorexia and also facilitated a substrate for fenfluramine anorexia.
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology*; D004347:Drug Interactions; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology*; D008636:Mesencephalon / Q000187:drug effects*; D016627:Oxidopamine; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects
D002395:Catecholamines; D006892:Hydroxydopamines; D011985:Receptors, Serotonin; D005277:Fenfluramine; D016627:Oxidopamine; D003913:Dextroamphetamine