The modulation of dopamine release by presynaptic nicotinic receptors in vitro is well established, but the significance of this effect in vivo is unclear. We have characterised the effect of nicotine, locally applied via a microdialysis probe, on dopamine release from the terminal regions of three ascending dopaminergic pathways in conscious, freely moving rats. Nicotine caused a dose-dependent increase in dopamine release in the striatum, the nucleus accumbens, and, to a lesser extent, the frontal cortex. Metabolite levels were unaltered by any concentration of nicotine. Prior administration of mecamylamine via the probe abolished the nicotineevoked increase in dopamine release, confirming the mediation of nicotinic receptors. The dose dependence of mecamylamine-sensitive, nicotine-evoked dopamine release was similar in all three brain regions. However, io-M tetrodotoxin totally blocked nicotine-stimulated dopamine release in the striatum and the accumbens but not the cortex. Daily subcutaneous injections of nicotine (0.4 mg kg 1 for 7 days) increased the response to a subsequent local application of nicotine in the striatum, and a similar trend was found in the other brain areas. The same daily dose of nicotine given as a continuous infusion had no effect, whereas infusion of 4mg kg1 day1 increased the response to a subsequent nicotine challenge. The localisation and regulation of nicotinic receptors in the terminal fields of dopaminergic pathways are discussed.

A wide diversity of animal models has been used to examine antidepressant activity. These range from relatively simple models sensitive to acute treatment, to highly sophisticated models that reputedly model some aspect of depressive illness and which yield a positive response to prolonged, chronic, drug treatment. In recent years antidepressant drug research has focused on the search for antidepressant therapy that has a more rapid onset of action. To be relevant, therefore, animal models must measure the time course of drug action. This review examines the claims of animal models to be sensitive to chronic drug treatment and considers their relevance. First, the review addresses the criteria necessary to examine the validity of animal models of depressive illness. Second, those animal models sensitive to chronic antidepressant treatment are reviewed with respect to their validity as animal models of either depressive illness and/or antidepressant activity. In particular, the development and utility of two "ethologically-relevant" animal models, the resident-intruder and social hierarchy paradigms, are described in detail. These models of rodent social and agonistic behaviour demonstrate that acute and chronic treatment with antidepressant drugs (regardless of their acute pharmacological activity) induce diametrically opposite changes in rodent agonistic behaviour. It is argued that the common ability of chronic treatment to increase rodent aggression (which in turn results in increased hierarchical status in closed social groups) most likely reflects the increased assertiveness and associated externalization of emotions expressed during recovery from depressive illness. Finally, findings that relate observed behavioural changes to underlying neurochemical changes are briefly reviewed.

This study, using a postal questionnaire, investigated the involvement of 534 community pharmacists with patients suffering from schizophrenia. The majority of the 236 respondents regularly dispensed medication for patients with schizophrenia and almost three-quarters had been asked for advice about medication from such patients or their carers. However, the majority of respondents believed that the advice they could give to these patients was limited by their knowledge of schizophrenia (86 per cent) and of therapeutics (70 per cent).Other perceived constraints to giving advice included lack of contact with other health professionals, poor communication skills and lack of experience in dealing with the mentally ill. Respondents were significantly less confident about advising patients with schizophrenia than advising other patient groups. The results suggest that there is a need to encourage community pharmacists' participation in continuing education and to improve liaison with other community health professionals such as community psychiatric nurses.

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