Adenosine plays a key role in the regulation of tissue oxygenation, neuronal firing, and neurotransmitter release. Four receptor subtypes have been identified and cloned: A(1), A(2A), A(2B), and A(3), although only A(1) and A(2A) receptors are prominent in rat brain. Much evidence now indicates that A(2A) receptors (A(2A)R) are highly enriched within striatal medium-sized spiny GABAergic neurons where they are closely associated with, and modulate, D(2)-dopaminergic receptors involved in motor control and reward behaviors. There is also consensus that A(2A)R are present in the nucleus accumbens and olfactory tubercle where they have been postulated to interact with prostaglandins in the regulation of sleep. There is less agreement as to whether or not A(2A)R are present in other brain regions. The present study describes an autoradiographic procedure that utilizes [(3)H]ZM-241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-alpha][1,3,5]triazin-5-ylamino]ethyl)phenol), a highly selective A(2A)-receptor ligand. Saturable specific binding was found in the rat caudate putamen with a K(d)=1.1 nM and B(max)=1150 fmol/mg. Binding was also found in the nucleus accumbens and the olfactory tubercle, but was not detected in extra-striatal brain regions.

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Gabapentin is a new adjunctive medication t o antiseizure therapies. Anecdotal evidence suggests that it may also help to alleviate mood symptoms in patients with bipolar illness.An open-label study examined the effects of adjunctive gabapentin in bipolar patients with mixed symptoms who had previously demonstrated only partial treatment responses. Mood ratings and side-effect profiles were followed weekly in 10 patients for 1 month. Decreases in Hamilton depression (P < 0.05) and Bech mania ratings (P < 0.01) were evident in the first week of treatment and were sustained. Potent early improvements were noted in early, middle, and late insomnia. The results suggest'that gabapentin may be of benefit to bipolar patients who only partially respond to other mood stabilizers. A favorable side-effect profile and rapid action make this drug an attractive choice as an adjunctive therapy.

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