Chronic ethanol attenuates circadian photic phase resetting and alters nocturnal activity patterns in the hamster

Abstract

Acute ethanol (EtOH) administration impairs circadian clock phase resetting, suggesting a mode for the disruptive effect of alcohol abuse on human circadian rhythms. Here, we extend this research by characterizing the chronobiological effects of chronic alcohol consumption. First, daily profiles of EtOH were measured in the suprachiasmatic nucleus (SCN) and subcutaneously using microdialysis in hamsters drinking EtOH. In both cases, EtOH peaked near lights-off and declined throughout the dark-phase to low day-time levels. Drinking bouts preceded EtOH peaks by approximately 20 min. Second, hamsters chronically drinking EtOH received a light pulse during the late dark phase [Zeitgeber time (ZT) 18.5] to induce photic phase advances. Water controls had shifts of 1.2 +/- 0.2 h, whereas those drinking 10% and 20% EtOH had much reduced shifts (0.5 +/- 0.1 and 0.3 +/- 0.1 h, respectively; P < 0.001 vs. controls). Third, incremental decreases in light intensity (270 lux to 0.5 lux) were used to explore chronic EtOH effects on photic entrainment and rhythm stability. Activity onset was unaffected by 20% EtOH at all light intensities. Conversely, the 24-h pattern of activity bouts was disrupted by EtOH under all light intensities. Finally, replacement of chronic EtOH with water was used to examine withdrawal effects. Water controls had photic phase advances of 1.1 +/- 0.3 h, while hamsters deprived of EtOH for 2-3 days showed enhanced shifts (2.1 +/- 0.3 h; P < 0.05 vs. controls). Thus, in chronically drinking hamsters, brain EtOH levels are sufficient to inhibit photic phase resetting and disrupt circadian activity. Chronic EtOH did not impair photic entrainment; however, its replacement with water potentiated photic phase resetting.

Fig. 1.

Histologically verified microdialysis probe tip locations relative to the SCN used in the ethanol (EtOH) pharmacokinetic analyses.

Fig. 2.

Twenty-four hour pharmacokinetics of EtOH in the suprachiasmatic nucleus (SCN) during forced 10% EtOH drinking. Dots represent means ± SE.

Fig. 3.

Composite 24-h pharmacokinetic profiles of SCN and subcutaneous EtOH superimposed with drinking and general locomotor activity rhythms from an individual hamster during forced 20% EtOH drinking. The black bar (top) represents the dark phase of the light-dark (LD) cycle.

Fig. 4.

Long-term EtOH drinking attenuates photic phase-advance responses to a dim (25 lux; left), but not to a bright (270 lux; right) light pulse delivered late in the dark phase [zeitgeber time (ZT) 18.5]. Bars with different letters are significantly different (P < 0.05). Bars represent means ± SE.

Fig. 5.

Representative double-plotted actograms of general locomotor activity showing EtOH inhibition of photic phase-advance responses to dim, but not to bright, light pulses delivered at ZT 18.5. Animals receiving a 25-lux light pulse: A: water-drinker. B: 10% EtOH-drinker. C: 20% EtOH drinker. Animals receiving a 270-lux light pulse: D: water-drinker. E: 20% EtOH drinker. Circled arrowheads denote the time of the light pulses.

Fig. 6.

Disruption of activity bout distribution during long-term 20% EtOH drinking. Under a 270-lux LD cycle (left), EtOH decreases the number of activity bouts during the night. Under a 0.5-lux LD cycle (right), the number of activity bouts is unaffected by EtOH consumption. Bars represent means ± SE. For each light intensity, bars with different letters are significantly different (P < 0.05).

Fig. 7.

Long-term EtOH consumption increases the average duration of activity bouts under 270 lux (left) and 0.5 lux (right) LD cycles. Bars represent means ± SE. For each light intensity, bars with different letters are significantly different (P < 0.05).

Fig. 8.

Representative double-plotted actograms of general locomotor activity at three light intensities. 270 lux: A: water-drinker; B: 20% EtOH-drinker. 5 lux: C: water-drinker; D: 20% EtOH-drinker. 0.5 lux: E: water-drinker; F: 20% EtOH drinker.

Fig. 9.

EtOH deprivation averaged over a 2- or 3-day interval potentiates phase-advance responses to a 25-lux light pulse at ZT 18.5. Bars represent means ± SE. Bars with different letters are significantly different (P < 0.05).

Fig. 10.

Representative double-plotted actograms of general locomotor activity showing phase-advance responses to a light pulse (25 lux) delivered at ZT 18.5 after 1, 2, and 3 days of EtOH deprivation. A: water-drinker; B: one-day EtOH deprivation; C: two-day EtOH deprivation; and D: three-day EtOH deprivation. Circled arrowheads denote the time of the light pulses.