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 was aimed at investigating 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 a1-h drinking session performed during the 12-h duration of 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 acutely 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.

Elevated reinforcing and motivational properties of alcohol at the end of the nocturnal period in sP rats

“…The results of the present study confirm, and extend to an operant procedure of alcohol self-administration, the results of two recent studies assessing alcohol intake in sP rats exposed, in their homecage, to daily drinking sessions of one hour with concurrent availability of multiple alcohol concentrations (0%, 10%, 20%, and 30%, v/v), unpredictable time schedule, and over the dark phase of the daily light/dark cycle (Colombo et al 2014; 2015). Alcohol intake was indeed highly sensitive to time schedule, as it rose progressively from 0.6–0.8 g/kg, when alcohol was made available during one of the first hours (1 st and 2 nd hour) of the dark phase, to ≥2 g/kg, when alcohol was made available during one of the latest hours of the dark phase (11 th and 12 th hour) (Colombo et al 2014; 2015).…”

“…Alcohol intake was indeed highly sensitive to time schedule, as it rose progressively from 0.6–0.8 g/kg, when alcohol was made available during one of the first hours (1 st and 2 nd hour) of the dark phase, to ≥2 g/kg, when alcohol was made available during one of the latest hours of the dark phase (11 th and 12 th hour) (Colombo et al 2014; 2015). Alcohol intake at the 12 th hour of the dark phase was associated to mean BALs of 100 mg% and signs of intoxication, leading us to propose that experimental procedure as a rodent model of binge drinking (Colombo et al 2014).…”

“…This lab is currently undertaking a series of experiments to possibly unravel the mechanism underlying the sensitivity to time schedule of alcohol drinking (Colombo et al 2014; 2015) and alcohol self-administration (present study) in sP rats. A recently collected set of data suggests that expectation of alcohol availability, generated by the unpredictable schedule of alcohol access, likely produces an emotional “distress” that increases progressively as time elapses over the dark phase: indeed, sP rats initially exposed to several, daily drinking sessions with unpredictable time schedule and then to the Social Interaction (SI) test (with no alcohol available on the day of the SI test) displayed higher levels of anxiety-related behaviors at the 12 th rather than 1 st hour of the dark phase (Colombo et al 2015).…”

“…Chambers were arranged to replicate the 4-bottle choice procedure of the previous drinking studies (Colombo et al 2014; 2015). To this end, the front panel of each chamber was equipped with (a) one retractable response-lever, (b) the retractable spouts of 3 sipper bottles (250-ml capacity) located outside the chamber, and (c) 3 stimulus lights (yellow, green, and light blue) mounted above the holes through which sipper spouts were made available.…”

“…This laboratory has recently proposed a new rodent model of binge-like drinking: when exposed to daily drinking sessions of one hour, with concurrent availability of multiple alcohol concentrations (0%, 10%, 20%, and 30%, v/v), and – most importantly – unpredictability of time of access to alcohol, selectively bred Sardinian alcohol-preferring (sP) rats consumed up to intoxicating amounts of alcohol and displayed high sensitivity to time schedule (Colombo et al 2014; 2015). Specifically, it was found that – as the time of alcohol access moved over the dark phase of the 12:12 hour light/dark cycle – alcohol intake increased progressively; when the drinking session occurred at the end of the dark phase, alcohol intake averaged ≥2 g/kg, resulted in blood alcohol levels (BALs) of approximately 100 mg% [meeting the criterion posed for binge drinking in humans (NIAAA 2004)], and produced severe motor-incoordination (Colombo et al 2014).…”