Anxiety-like behaviors at the end of the nocturnal period in sP rats with a "history" of unpredictable, limited access to alcohol

Abstract

Recent research found that exposure of selectively bred, Sardinian alcohol-preferring (sP) rats to multiple alcohol concentrations (10%, 20%, and 30%, v/v), under the 4-bottle "alcohol vs. water" choice regimen, in daily 1-h drinking sessions with an unpredictable time schedule, promoted high intakes of alcohol (≥2 g/kg) when the drinking session occurred over the final hours of the dark phase of the light/dark cycle. The present study investigated whether these high intakes of alcohol (a) were associated with alterations in rats' emotional state (Experiment 1) and (b) were pharmacologically manipulable (Experiment 2). In both experiments, over a period of 12 days, sP rats were initially exposed daily to a 1-h drinking session during the dark phase; time of alcohol exposure was changed each day and was unpredictable to rats. The day after this 12-day drinking phase, rats were (a) exposed to the Social Interaction (SI) test at the 1st or 12th hour of the dark phase with no alcohol available (Experiment 1) or (b) treated with the positive allosteric modulator of the GABAB receptor, GS39783 (0, 25, 50, and 100 mg/kg, intragastrically [i.g.]), and exposed to a drinking session at the 12th hour of the dark phase (Experiment 2). In Experiment 1, rats exposed to the SI test during the 12th hour spent approximately 35% less time in "social" behaviors than rats exposed to the SI test during the 1st hour. No difference in "social" behaviors was observed between alcohol-naive sP rats exposed to the SI test at the 1st and 12th hour. In Experiment 2, all doses of GS39783 selectively reduced alcohol intake. These results suggest that (a) expectation of alcohol availability likely exacerbated the anxiety-like state of sP rats and (b) the GABAB receptor is part of the neural substrate underlying these exceptionally high intakes of alcohol in sP rats.

Keywords: Anxiety-like behaviors; Experimental model of binge drinking; Limited and unpredictable access to alcohol; Positive allosteric modulator of the GABA(B) receptor, GS39783; Sardinian alcohol-preferring (sP) rats; Time schedule of alcohol drinking.

Fig. 1

Schematic representation of the experimental design of Experiments 1A and 2.

Fig. 2

Left panel: Alcohol intake in Sardinian alcohol-preferring (sP) rats exposed to 12 consecutive daily 1-h drinking sessions under the 4-bottle “alcohol (10%, 20%, and 30%, v/v) vs. water” choice regimen. Drinking sessions occurred during one of the 12 hours of the dark phase of the daily light/dark cycle; time of the drinking session was changed daily in a semi-random order and was unpredictable to rats. Each point is the mean ± SEM of n = 34 rats. Right panel: Time spent in social interaction (SI) behaviors by pairs of sP rats exposed to the SI test at the 1st or 12th hour of the dark phase of the day after completion of the above-mentioned 12-day drinking period. Alcohol was not available on the test day. Data were collected in two equal time intervals (0–5 and 6–10 min) of the 10-min session; the right portion of this panel depicts data from the total session (0–10 min). Each bar is the mean ± SEM of n = 8–9 rat pairs. *p < 0.05 and **p < 0.005 in comparison to the “1st-Hour” rat group of the corresponding time interval (Newman-Keuls test). §p < 0.01 in comparison to the “1st-Hour” rat group (t test).

Fig. 3

Time spent in social interaction (SI) behaviors by pairs of alcohol-naive sP rats exposed to the SI test at the 1st or 12th hour of the dark phase. Data were collected in two equal time intervals (0–5 and 6–10 min) of the 10-min session. The right portion of this panel depicts data from the total session (0–10 min). Each bar is the mean ± SEM of n = 12 rat pairs.

Fig. 4

Left panel: Alcohol intake in Sardinian alcohol-preferring (sP) rats exposed to 12 consecutive daily 1-h drinking sessions under the 4-bottle “alcohol (10%, 20%, and 30%, v/v) vs. water” choice regimen. Drinking sessions occurred during one of the 12 hours of the dark phase of the daily light/dark cycle; time of the drinking session was changed daily in a semi-random order and was unpredictable to rats. Each point is the mean ± SEM of n = 32 rats. Right panel: Effect of acute, intragastric administration of the positive allosteric modulator of the GABA_B receptor, GS39783, on alcohol intake in sP rats exposed to an additional drinking session conducted at the 12th hour of the dark phase of the day after completion of the above-mentioned 12-day drinking period. Each bar is the mean ± SEM of n = 8 rats. *p < 0.0005 in comparison to 0 mg/kg GS39783-treated rat group (Newman-Keuls test).