Neuropharmacology of appetite regulation.

Patient consultations concerning weight problems are frequent but the over-all response to drug treatment is poor. There are many so-called anorexic drugs but the range of unwanted actions is even larger and often with distressing results. The costs to the National Health Service of doctors prescribing appetite-suppressant drugs exceeded E3.5 m in 1975 but there is little evidence of proportional clinical benefit. Much of the pharmacological evidence relating to the central regulation of appetite derives from experimental studies with these same compounds. This review must therefore be read with two admonitions in mind: ( I ) there is no guarantee that the neuropharmacology described is relevant to the control of appetite in man, and (2) the biological models employed to predict anorexic activity in man are less than adequate. The governing role of the central nervous system in feeding behaviour is firmly established and the majority of studies identify the hypothalamus as the most important area. The stereotaxic instrument has provided the means of creating discrete lesions and permitting localized electrical or chemical stimulation within this region, the results affording direct and convincing evidence. Yet it is salutary to note that physiologists working in widely difkrent fields have come to similar conclusions about the location of their particular regulating centre. It is evident therefore that electrolytic lesions, electical stimulation or the placement of specific chemical substances may influence a wide variety of physiological variables of which feeding behaviour is but one. Specific interpretations of such experimental information may therefore be misleading. The elegant studies of B. K. Anand and J. R. Brobeck contributed greatly to present concepts of hypothalamic control of feeding behaviour (e.g. Brobeck, Tepperman & Long, 1947; Anand & Brobeck, 1951). In essence they showed that bilateral electrolytic lesions in the ventromedial nuclei produced hyperphagia: a period of voracious eating behaviour leading to gross obesity in the operated animals. Lesions of the lateral hypothalamus produce virtually opposite results, ablation resulting in aphagia to the point of death by starvation. Electrical stimulation of the same discrete areas has been found to yield similar results (Miller, 1960). Injections of gold thioglucose appear selectively to damage neurons in the ventromedial nuclei, also followed by hyperphagia and obesity (Drachman & Tepperman, 1954). Direct injections of putative neurotransmitters into the brain lends further evidence for the hypothalamic control of food intake (Grossman, 1962; Miller, 1965). Such experimental reports have led to the concept of a satiety