Functional implications of dopamine D1 vs. D2 receptors: A 'prepare and select' model of the striatal direct vs. indirect pathways.

The functions of the D1- and D2-dopamine receptors in the basal ganglia have remained somewhat enigmatic, with a number of competing theories relating to the interactions of the 'direct' and 'indirect pathways'. Computational models have been good at simulating properties of the system, but are typically divorced from the underlying neural architecture. In this article we propose a new model which re-addresses response selection at the level of the basal ganglia. At the core of this response selection system the D1 DA receptor-expressing striatal pathways 'prepare' the set of possible appropriate responses. The D2DR-expressing striatal pathways then shape and 'select' from this initial response set framework. This article is part of a Special Issue entitled: Ventral Tegmentum & Dopamine.

The Edinburgh cohort of HIV-positive injecting drug users at 10 years after infection: a case-control study of the evolution of dementia.

OBJECTIVE: To examine the evolution of dementia in HIV-positive injecting drug users (IDU) in Edinburgh. DESIGN: Case-control study. PARTICIPANTS: Twenty six (6%) out of 404 patients in the Edinburgh cohort of HIV-positive IDU who have developed HIV-1-associated dementia in the 10 years since infection and seroconversion. METHODS: Patients were tested repeatedly, where possible, on a range of neuropsychological and neurophysiological measures. The results from patients with dementia were compared with those of age, sex and IQ-matched non-demented HIV-positive controls from the cohort. An auditory event-related potential (P3 or P300), a neurophysiological measure of cognitive function, detected the onset of a marked slowing of cognitive and psychomotor functions. Neuropsychological measures that involve the speed of information processing such as the Trail-Making task also identified the early stages of dementia. RESULTS: Dementia was associated with a more advanced stage of systemic disease, increased rates of decline in CD4 cell counts and markedly reduced survival compared with the non-demented controls. No evidence for a protective effect of treatment with zidovudine was detected. CONCLUSION: In the first 10 years after infection with HIV-1 dementia is an individual development, not the clinical extreme of general intellectual impairment, and had occurred in at least 6% of our IDU cohort. Future questions concern the long-term rate of dementia, the critical neuropathological change and the true potential for early treatment.