1 The sympathetic noradrenergic activation of brown adipose tissue and the biochemical mechanisms involved in diet-induced thermogenesis were studied in rats. 2 A close correlation was found between brown adipose tissue Na+, K+-
adenosinetriphosphatase (Na+, K+-
ATPase) activity in vitro and in vivo measurements of resting oxygen consumption (VO2). The effects of
noradrenaline on in vitro NA+, K+-
ATPase activity in brown adipose tissue and in vivo VO2 could be mimicked by a variety of agents. These included beta-
adrenoceptor agonists and agents known to induce the release of
noradrenaline or inhibit the
noradrenaline uptake process. The pharmacological evidence suggests that dopaminergic mechanisms may also be involved in the control of thermogenesis. 3
Amphetamine did not increase VO2 in rats without causing associated increases in locomotor activity.
Ciclazindol at doses of 3-30 mg/kg intraperitoneally increased VO2 but did not appear to increase locomotor activity or evoke any other signs of CNS stimulation including lengthening of time to sleep onset or stereotypy. Separation of metabolic and CNS effects occurred only at the lowest dose of
mazindol used (0.3 mg/kg i.p.). These results are probably a reflection of (a) the relative abilities of these drugs to inhibit brain and brown adipose
noradrenaline uptake processes and (b) the relatively high accumulation of
ciclazindol in brown adipose. 4 Of the drugs tested, only
ciclazindol was a more potent inhibitor of the
noradrenaline uptake system in brown adipose tissue (BAT) than in brain. Kinetic analysis also revealed that the actions of
ciclazindol on the NA uptake system and Na+, K+-
ATPase in BAT differed from those of
mazindol. 5 These findings suggest that
ciclazindol may produce an energy wasting effect in rodents without causing overt CNS stimulation; the implications of these findings in terms of human
obesity are discussed.