6-Hydroxydopamine-induced blockade of hypothalamic obesity: critical role of brain dopamine-norepinephrine interaction.
1. Adult female rats received 3 weekly intracisternal injections of 6-hydroxydopamine or ascorbic acid vehicle following systemic pretreatment with desipramine or pargyline to deplete brain dopamine alone or in combination with norepinephrine. 2. Three weeks after the last injection, all rats received bilateral radiofrequency lesions of the medial hypothalamus to induce overeating and obesity. 3. Compared to normal controls, all lesioned groups over ate and became equally obese except the group receiving desipramine + 6-hydroxydopamine, which failed to show either response. 4. Terminal assays of striatal and neocortical monoamines revealed that hypothalamic obesity was blocked only when dopamine was selectively depleted, but not when equivalent dopamine depletion occurred with concurrent norepinephrine depletion. 5. The ability of central 6-hydroxydopamine to block hypothalamic obesity seems due to an imbalance created in the neural interactions of brain dopamine and norepinephrine systems.
D000818:Animals; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004435:Eating / Q000187:drug effects*; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology*; D007033:Hypothalamus, Middle / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects
D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D016627:Oxidopamine; D010293:Pargyline; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine