The effects of ethanol are biphasic with respect to administration time. Positive reinforcement occurs early as blood ethanol levels rise. As these levels fall, the depressant and aversive properties predominate. This time-dependency supports a multi-phasic view of ethanol's effects in the CNS in which ethanol has distinct actions within independent brain systems as a function of time after ethanol administration. Seeking evidence of ethanol-induced changes in disparate neural systems as a function of time, the present proposal will determine whether ethanol affects different neural substrates at different times after ethanol administration and whether these systems adapt to chronic ethanol exposure at different rates. Brain mapping studies are in a unique position to contribute significantly in this regard because they determine levels of activity throughout the brain simultaneously. This laboratory has recently shown that ethanol's effects on functional brain activity in the rat are also time-dependent. Activity was altered immediately after ethanol administration in one set of structures, and activity was altered in a completely different set of structures as blood ethanol levels fell. Therefore, it appears that different neural circuits subserve the effects of ethanol when concentrations are rising and falling. The proposed studies will first extend our previous findings obtained at a single dose to a range of relevant doses in order to establish the conditions of dose and time under which each of these two patterns of brain energy metabolism occur. We also present preliminary data which suggest that functional activity adapts differently to chronic ethanol in distinct sets of brain structures in the rat. Therefore, the present studies will also determine how regional neural activity along the rising and falling phases of the blood ethanol curve change in response to chronic exposure to ethanol. These finding swill contribute to the body of work that supports a concept of tolerance which recognizes that integrated activity among various neural circuits are responsible for the time-dependent effects of ethanol.
