Neonatal alcohol exposure permanently disrupts the circadian properties and photic entrainment of the activity rhythm in adult rats.

Alcohol exposure during critical stages of development induces structural and cellular damage within the central nervous system. Detailed studies using a rat model indicate that alcohol exposure during the brain growth spurt (early postnatal period), which is equivalent to the period of human brain development during the third trimester (Dobbing and Sands, 1979), produces a wide range of damaging effects, including reductions in brain size and weight (Maier et al., 1996), cell loss in discrete brain regions such as the cerebellum, hippocampus, and olfactory bulb (Bonthius et al., 1992; Bonthius and West 1990; Chen et al., 1998; Goodlett et al., 1998), altered neuronal circuitry (West et al., 1981), and decreased expression of specific neurochemical signals (Manteuffel, 1996). In many instances, this alcohol-induced injury to specific brain regions is permanent and thus may have long-term consequences in the neural regulation of behavior. In rats exposed to alcohol during the early postnatal period, the cerebellum and hippocampus provide notable examples where alcohol-induced cell loss is, respectively, coupled with behavioral deficits on motor performance and learning/memory tasks (Goodlett et al., 1987, 1988; Kelly et al., 1988; Thomas et al., 1996, 1998). However, further analysis is necessary to delineate the full extent of the long-term neurobehavioral disturbances associated with the damaging effects of developmental alcohol on specific brain regions. The neural center responsible for the regulation of circadian or 24-hr rhythms has been recently identified as another target for alcohol-induced insult during central nervous system development (Earnest et al., 2001). In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as a biological clock that governs the generation of circadian rhythms in a variety of biological processes and their synchronization or entrainment to light-dark cycles (Moore, 1983). Exposure to alcohol during the early postnatal period has been shown to disrupt the circadian rhythm in SCN content of brain-derived neurotrophic factor in adult rats (Allen et al., 2004). Consistent with the effect of alcohol on this SCN output signal, preliminary studies suggest that developmental alcohol exposure also induces permanent alterations in SCN molecular oscillations that comprise the circadian clock mechanism (Farnell et al., 2004b). Because disruption of endogenous SCN rhythmicity can produce tangible changes in the circadian regulation of behavior (Reppert and Weaver, 2001), it is possible that alterations in circadian behavior may accompany developmental alcohol-induced effects on the SCN clockworks and its circadian output signals. On the basis of clinical evidence linking maternal alcohol consumption during pregnancy to sleep-wake disturbances in offspring (Rosett et al., 1979; Steinhausen and Spohr, 1998; Steinhausen et al., 1993), the present study used a rat model to determine whether alcohol exposure during the brain growth spurt also causes long-term changes in the circadian rhythm of wheel-running behavior. Specifically, we examined the effects of neonatal alcohol exposure on the quantitative parameters, light-dark entrainment and circadian regulation of wheel-running activity, in adult rats.