Catecholaminergic mechanisms of the lateral hypothalamus: their role in the mediation of amphetamine anorexia.
The brain mechanisms mediating amphetamine's suppressive effect on feeding behavior were analyzed in rats with chronically implanted brain cannulas. Experiments in which drugs were injected directly into the anterolateral hypothalamus, the region found to be most responsive to amphetamine's action, yielded the following results. (1) Over a dose range of 6.25 nmoles (0.8 mug) to 400 nmoles (51.4 mug), hypothalamically injected D-amphetamine produced a reliable suppression of food consumption (20 percent at 6.25 nmoles, increasing to 88 percent at 200 nmoles) and was found to be approximately 3 times as potent as L-amphetamine in yielding this effect. (2) The anorexic effect of hypothalamically injected D-amphetamine was totally abolished by local administration of alpha-methyltyrosine, an inhibitor of dopamine, norepinephrine, and perhaps epinephrine synthesis, or by local administration of Fla-63, an inhibitor of only norepinephrine, and perhaps epinephrine, synthesis. (3) This effect of hypothalamic D-amphetamine was also antagonized by locally administered dopaminergic or beta-adrenergic receptor blockers but was unaffected by alpha-adrenergic, serotonergic, and cholinergic blockers. (4) Lateral hypothalamic administration of dopaminergic or beta-adrenergic receptor blockers, at quite low doses, was also effective in antagonizing the anorexia induced by peripherally administered D-amphetamine. These results strongly suggest that amphetamine, in suppressing feeding behavior, acts through the lateral hypothalamus, perhaps the anterior region, causing a release of dopamine and norepinephrine (or perhaps epinephrine) from lateral hypothalamic nerve endings and a subsequent stimulation of dopaminergic and beta-adrenergic receptors located in that region.
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001285:Atropine / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002928:Cinanserin / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D014043:Tolazoline / Q000494:pharmacology
D002395:Catecholamines; D008781:Methyltyrosines; D010868:Pimozide; D003533:Cyproheptadine; D001285:Atropine; D011433:Propranolol; D014043:Tolazoline; D000661:Amphetamine; D006220:Haloperidol; D002928:Cinanserin; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine