Although oral squamous cell carcinoma accounts for only a small proportion of malignant neoplasms in the UK, oral cancer incidence and mortality rates have been rising in recent years. The natural history of oral cancer is not adequately understood at present and there is very little information about the epidemiology of precancerous lesions in the UK. There are also insucient data to provide ®rm evidence that the percentage of cases arising de novo is greater in the UK and the Western world as compared to the Indian subcontinent. Screening for oral cancer by visual examination is simple, inexpensive and causes little discomfort; however, there is no evidence for the eectiveness of screening for oral cancer either in reducing mortality from the disease or in reducing the incidence of invasive disease by detection and treatment of precancerous lesions. There is currently insucient evidence to recommend population screening for oral cancer in the UK. Measures aimed at primary prevention of the disease may be a more feasible method of disease control at present. #

Glial cell line-derived neurotrophic factor (GDNF) has been shown to be involved in the maintenance of striatal dopaminergic neurons. Neurotrophic factors are crucial for the plasticity of central nervous system and may be involved in long-term responses to drug exposure. To study the effects of reduced GDNF on dopaminergic behaviour related to addiction, we compared the effects of morphine on locomotor activity, conditioned place preference (CPP) and extracellular accumbal dopamine in heterozygous GDNF knockout mice (GDNF1/2) with those in their wild-type (Wt) littermates. When morphine 30 mg/kg was administered daily for 4 days, tolerance developed towards its locomotor stimulatory action only in the GDNF1/2 mice. A morphine 5 mg/kg challenge dose stimulated locomotor activity only in the GDNF1/2 mice withdrawn for 96 h from repeated morphine treatment, whereas clear and similar sensitization of the locomotor response was seen after a 10 mg/kg challenge dose in mice of both genotypes. Morphine-induced CPP developed initially similarly in Wt and GDNF1/2 mice, but it lasted longer in the Wt mice. The small challenge dose of morphine increased accumbal dopamine output slightly more in the GDNF1/2 mice than in the Wt mice, but doubling the challenge dose caused a dose-dependent response only in the Wt mice. In addition, repeated morphine treatment counteracted the increase in the accumbal extracellular dopamine concentration we previously found in drug-naive GDNF1/2 mice. Thus, reduced endogenous GDNF level alters the dopaminergic behavioural effects to repeatedly administered morphine, emphasizing the involvement of GDNF in the neuroplastic changes related to long-term effects of drugs of abuse.