Assessment of the interoceptive effects of alcohol in rats using short-term training procedures

Abstract

In the present study, we sought to determine whether the interoceptive effects of alcohol (1 g/kg, IG) could be assessed using a Pavlovian discrimination method, in which the alcohol drug state sets the occasion for which an environmental stimulus (e.g., light) will be followed by a sucrose reward. This procedure takes advantage of a naturally occurring behavior (i.e., food-seeking) which can be trained rapidly prior to the initiation of discrimination training. Given that the interoceptive effects of alcohol are routinely assessed using operant drug discrimination methods, another group of rats was trained using standard two-lever operant drug discrimination procedures in an effort to compare the Pavlovian procedure to a known behavioral benchmark. The results from this work show that, in addition to operant discrimination procedures, a Pavlovian discrimination task can be used to evaluate the interoceptive effects of alcohol. In addition to the brief behavioral sucrose access training (3 days) required prior to the initiation of the Pavlovian discrimination, the alcohol discrimination was acquired relatively rapidly (i.e., 8 training sessions), shortening the overall duration of the experiment. These features of the Pavlovian procedure make it a valuable method by which to assess the interoceptive effects of alcohol if a short experimental time frame is required, such as assessing the interoceptive effects of alcohol during a brief developmental window (e.g., adolescence) or determining the effects of a pretreatment (i.e., chronic stress, chronic drug pretreatment) on the acquisition of the alcohol discrimination. As such, this initial characterization confirms the feasibility of using this Pavlovian discrimination training method as an additional tool by which to assess the interoceptive effects of alcohol, as there may be experimental situations that necessitate short term discrimination training.

The nicotine + alcohol interoceptive drug state: contribution of the components and effects of varenicline in rats

“…Rats were trained using the same behavioral chambers and procedures were similar to those described in detail in (Besheer et al 2012). Additionally, chambers were outfitted with infrared photobeams (that divided the chamber into 4 parallel zones) to measure locomotor activity during sessions (number of beam breaks).…”

“…For test sessions, onset of light presentation was randomized and varied from 45-105 seconds into the 2 minute test period. For Experiments 1 and 2, cumulative dosing procedures were used as we describe in (Besheer et al 2012; 4 separate tests conducted in succession such that testing of the stated dose curve completed in ~48 min). For Experiment 3, single test sessions were used.…”

“…The N+A solution was administered IG, with volumes varied by weight to obtain the desired doses. Nicotine and alcohol doses were based on previous drug discrimination literature for each alone and in combination (Besheer et al 2012; Charntikov et al 2014; Ford et al 2012; Gauvin and Holloway 1993; Pittenger and Bevins 2013; Pittenger et al 2015; Polewan et al 2013; Quertemont and Grant 2002; 2004; Quertemont et al 2003; Troisi et al 2013). Varenicline (Abcam Pharmaceuticals) dose and pretreatment interval were chosen based on previous studies (Ginsburg and Lamb 2013; Randall et al 2015).…”

“…Consequently, the drug state comes to modulate behavior as evidenced by increased anticipatory reward-seeking during the cue light (i.e., head entries into a liquid receptacle; “goal-tracking”) on drug training sessions. These procedures have been used to characterize the interoceptive effects of several drugs including alcohol, amphetamine, caffeine, methamphetamine, and nicotine (Besheer et al 2012; Murray et al 2007; Palmatier et al 2004; Palmatier et al 2005; Reichel et al 2007). Furthermore, the opposite association can also be trained, such that the drug state can signal the absence of reward (i.e., assessment of subject’s ability to withhold behavior).…”

Influence of sensitization on the discriminative stimulus effects of methylphenidate in mice

“…Alternatively, rather than using a procedure that relies on negative reinforcement, another strategy might be to use the discriminative stimulus of MPH as an occasion setter predicting when a discrete cue signals delivery (or not) of a reinforcer such as sucrose. Such Pavlovian conditioning procedures can be rapidly trained and have been demonstrated for drugs like alcohol (Besheer et al , 2012) and nicotine (Besheer et al , 2004; Palmatier et al , 2004). Strategies like these may prove useful in future studies that examine the influence of drug exposure outside of the training context on the discriminative stimulus control of reinforced behavior by abused drugs.…”