Lack of synergistic feeding enhancement by systemic clonidine and 8-OH-DPAT

To expand on recent suggestions that brain alpha 2-adrenergic and serotonergic systems may interact in their controls over feeding, three experiments were conducted to determine if combining clonidine and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) injections subcutaneously might produce exponential feeding enhancements greater than responses elicited by either agent alone. Ad lib fed adult male rats were tested in 2 x 2 drug designs in all studies. In Experiment 1, 30 micrograms/kg clonidine reliably enhanced feeding over a 6-hr test period. However, 250 micrograms/kg 8-OH-DPAT showed no signs of enhancing this response, but instead seemed to impede it as determined by analyses of cumulative intake curves. In Experiment 2, either 10 micrograms/kg clonidine or 250 micrograms/kg 8-OH-DPAT reliably enhanced 6-h interval intakes, but their combination again failed to synergize other than to interact with time in suppressing intake. To determine if feeding synergy might occur if subthreshold doses of each agent were combined, Experiment 3 tested 1 microgram/kg clonidine and 15 micrograms/kg 8-OH-DPAT in 4-h feeding tests. Neither agent alone elicited reliable feeding as planned, but their combination also failed to stimulate feeding. These findings, combined with other recent work, do not support the possibility that previously demonstrated interactions between brain alpha 2-adrenergic and serotonergic systems extend to circumstances wherein enhancements of the former combined with suppressions of the latter might underly robust overeating responses.