Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure

Abstract

Chronic alcohol (EtOH) binging has been associated with long-term neural adaptations that lead to the development of addiction. Many of the neurobiological features of EtOH abuse are shared with other forms of binging, like pathological feeding. The drinkingin-the-dark paradigm (DID) has been used extensively to study the neurobiology of EtOH binge-like drinking due to its ability to promote high intakes relevant to human behavior. DID can also generate high consumption of other tastants, but this procedure has not been fully adapted to study forms of binging behavior that are not alcohol-driven. In the present study we used a modified version of DID that uses multiple bottle availability to promote even higher levels of EtOH drinking in male C57BL/6J mice and allows a thorough investigation of tastant preferences. We assessed whether administration of systemic naltrexone (NTX) could reduce binging on EtOH, sucrose, and saccharin separately as well as in combination. Our multiple bottle DID procedure resulted in heightened levels of consumption compared to previously reported data using this task. We found that administration of the opioid receptor antagonist NTX reduced intakes of preferred, highly concentrated EtOH, sucrose, and saccharin. We also report that NTX was able to reduce overall intakes when animals were allowed to self-administer EtOH, sucrose, or saccharin in combination. Our modified DID procedure provides a novel approach to study binging behavior that extends beyond EtOH to other tastants (i.e., sucrose and artificial sweeteners), and has implications for the study of the neuropharmacology of binge drinking.

Targeting diacylglycerol lipase reduces alcohol consumption in preclinical models

“…In line with our data, DAGL inhibition by DO34 has been previously shown to reduce operant responding for alcohol (43). The magnitude of effect on EtOH intake observed after DAGL inhibition is comparable to or greater than those observed with clinically available treatments such as Naltrexone (44)(45)(46) and Acomprasate (46,47) in similar rodent models. Moreover, pharmacological DAGL inhibition did not affect sucrose preference, suggesting a lack of generalized effect to natural reward, although female DAGL KO mice do exhibit reductions in sucrose preference under some conditions (23).…”

Sucrose-based flavor preferences in rats: Factors affecting detection of extinction.

“…Our preferred explanation is in terms of context shift, as outlined previously. A less interesting alternative is that, when two bottles are used, rats drink more, as found in both previous studies (e.g., Morales et al, 2020;Tordoff, 2002) and in the present Experiment 4 (see Figure 10); greater intakes mean greater exposure to the to-be-extinguished flavor.…”

“…The availability of multiple bottles containing taste solutions has been found to increase voluntary intakes of solutions such as sucrose, saccharin, and ethanol in rats and mice (Morales et al, 2020; Tordoff, 2002). Rodent drinking behavior appears to be stimulated by multiple sources of a tastant as the animals sample from all sources available.…”

The serotonin 2C receptor agonist lorcaserin, alone and in combination with the opioid receptor antagonist naltrexone, attenuates binge‐like ethanol drinking

“…Lorcaserin and naltrexone reduce consumption of a range of food types 32,34,36,37 including liquids, such as sucrose and saccharin as shown here. They also alter intravenous self‐administration of cocaine and opioids 13,14,38 in rats.…”