Ethical issues in neuroscience research on substance dependence treatment and prevention

Previous chapters have presented the latest findings in neuroscience research, and have pointed to potential treatment and prevention strategies. However, there are many ethical implications of the research itself, as well as the treatment and prevention strategies, that must be considered. The rapid pace of change in the field of neuroscience brings with it a host of new ethical issues, which need to be addressed. This chapter considers the important ethical and human rights issues that are raised by neuroscience research on psychoactive substance dependence.

Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment

OBJECTIVE: To observe the chronic effects of human growth hormone (hGH) and AOD9604 (a C-terminal fragment of hGH) on body weight, energy balance, and substrate oxidation rates in obese (ob/ob) and lean C57BL/6Jmice. In vitro assays were used to confirm whether the effects of AOD9604 are mediated through the hGH receptor, and if this peptide is capable of cell proliferation via the hGH receptor. METHOD: Obese and lean mice were treated with hGH, AOD or saline for 14 days using mini-osmotic pumps. Body weight, caloric intake, resting energy expenditure, fat oxidation, glucose oxidation, and plasma glucose, insulin and glycerol were measured before and after treatment. BaF-BO3 cells transfected with the hGH receptor were used to measure in Vitro I-125-hGH receptor binding and cell proliferation. RESULTS: Both hGH and AOD significantly reduced body weight gain in obese mice. This was associated with increased in vivo fat oxidation and increased plasma glycerol levels (an index of lipolysis). Unlike hGH, however, AOD9604 did not induce hyperglycaemia or reduce insulin secretion. AOD9604 does not compete for the hGH receptor and nor does it induce cell proliferation, unlike hGH. CONCLUSIONS: Both hGH and its C-terminal fragment reduce body weight gain, increase fat oxidation, and stimulate lipolysis in obese mice, yet AOD9604 does not interact with the hGH receptor. Thus, the concept of hGH behaving as a pro-hormone is further confirmed. This data shows that fragments of hGH can act in a manner novel to traditional hGH-stimulated pathways.

Specific manipulative therapy treatment for chronic lateral epicondylalgia produces uniquely characteristic hypoalgesia

The treatment of lateral epicondylalgia, a widely-used model of musculoskeletal pain in the evaluation of many physical therapy treatments, remains somewhat of an enigma. The protagonists of a new treatment technique for lateral epicondylalgia report that it produces substantial and rapid pain relief, despite a lack of experimental evidence. A randomized, double blind, placebo-controlled repeated-measures study evaluated the initial effect of this new treatment in 24 patients with unilateral, chronic lateral epicondylalgia. Pain-free grip strength was assessed as an outcome measure before, during and after the application of the treatment, placebo and control conditions. Pressure-pain thresholds were also measured before and after the application of treatment, placebo and control conditions. The results demonstrated a significant and substantial increase in pain-free grip strength of 58% (of the order of 60 N) during treatment but not during placebo and control. In contrast, the 10% change in pressure-pain threshold after treatment, although significantly greater than placebo and control, was substantially smaller than the change demonstrated for pain-free grip strength. This effect was only present in the affected limb. The selective and specific effect of this treatment technique provides a valuable insight into the physical modulation of musculoskeletal pain and requires further investigation. (C) 2001 Harcourt Publishers Ltd.

An integrative approach for studying the etiology of alcoholism and other addictions

Studies of alcoholism etiology often focus on genetic or psy-chosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions — behavioral undercontrol, pharmacologic vulnerability, negative affect regulation — addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.