Adenosine and brain function

Adenosine is an endogenous neuromodulator that influences many functions in the central nervous system (CNS). The levels of adenosine increase when there is an imbalance between rates of energy use and rates of energy delivery. Thus, increased neuronal activity, and particularly hypoxia or ischemia, results in markedly elevated levels of adenosine (Newby, 1991). Because adenosine tends to reset the energy balance, it has been called a retaliatory metabolite (Newby, 1984), and its potential role as an endogenous neuroprotective agent both in ischemia and following seizures has been repeatedly emphasized (de Mendonça et al., 2000; Dunwiddie and Masino, 2001; Fredholm, 1996; Marangos, 1991; Marangos et al., 1990; Phillis and Goshgarian, 2001; Picano and Abbracchio, 2000; Rudolphi et al., 1992b; Von Lubitz, 2001). Another major impetus for studies of the role of adenosine in brain function has been the realization that many of the effects of the most widely used of all psychoactive compounds, caffeine, is exerted by blocking effects of adenosine (Daly, 1977; Fredholm, 1980; Fredholm et al., 1999; Sattin and Rall, 1970). As discussed later in this chapter, one important implication of this is that at least some effects of adenosine are exerted already under basal conditions. Over the past decade, studies with pharmacological tools and using genetically modified mice have revealed other roles of adenosine. This chapter examines some of these, but the interested reader is referred to other reviews, cited where appropriate, to get a more complete picture. © 2005 Elsevier Inc. All rights reserved.