Dopamine-norepinephrine interactions in the development of hyperphagia and obesity following medial hypothalamic...

Conflicting evidence exists on the ability of central 6-hydroxydopamine (6-OHDA) injections to alter the subsequent development of hyperphagia and obesity following medial hypothalamic lesions (MHL) in rats. An initial study found no effects of prior intracisternal (IC) 6-OHDA on the subsequent development of this MHL syndrome, while later work reported that a dopamine (DA) depletions induced by intracerebral 6-OHDA effectively blocked it. The present study reexamined this issue by investigating the effects of depleting brain dopamine, norepinephrine (NE), or both DA and NE, on overeating and obesity induced by subsequent MH lesions. Different patterns of DA and NE depletions were achieved by IC 6-OHDA in combination with systemic pretreatments designed to protect central NE, DA, or neither amine, respectively. It was found that 6-OHDA regimens that selectively depleted forebrain DA did prevent the development of hyperphagia and obesity following MHL. However, when such forebrain DA depletions were accompanied by NE depletions no such blockade occurred. Manipulations which selectively depleted forebrain NE had no effect on MHL-induced hyperphagia and obesity. These results offer a framework for resolving previous discrepancies in the literature concerning brain monoamines and MHL effects. They also indicate that the effectiveness of brain DA depletions in blocking the MHL syndrome is critically dependent on the functional status of NE systems.