Baclofen reduces fat intake under binge-type conditions

Abstract

The GABA-B agonist baclofen reduces drug self-administration in rats and has shown promise clinically in the treatment of substance abuse. Baclofen generally does not reduce food intake in non-binge feeding protocols. In this study, baclofen was tested in a fat-binge protocol. Thirty male rats were divided into three groups (B: binge; FM: fat-matched; C: chow). B received a bowl of vegetable shortening for 2 h on Monday, Wednesday, and Friday (MWF) and continuous access to powdered chow (regular chow) in all phases. FM had continuous access to a regular chow+shortening mixture (FM chow) that provided the same proportion of shortening and regular chow that the B rats consumed in all phases. In addition, FM had the following: phase 1: no separate bowl of shortening; phase 2: 2-h MWF access to a separate bowl of shortening; phase 3, daily 2-h access to a separate bowl of shortening; C rats had continuous access to the regular chow in all phases. In addition, C had the following: phase 1: no separate bowl of shortening; phase 2: 2-h MWF access to a separate bowl of shortening; in phase 3, daily 2-h access to a separate bowl of shortening. Baclofen (1.0, 1.8 mg/kg, i.p.) reduced shortening intake regardless of access condition. Baclofen had no effect on, or stimulated, FM and regular chow intake. These results demonstrate that baclofen can reduce fat intake in rats under binge-type conditions. Furthermore, these results indicate that bingeing, as modeled in our protocol, is different from other forms of food intake and may share similarities with substance abuse.

Baclofen, raclopride, and naltrexone differentially reduce solid fat emulsion intake under limited access conditions

“…In addition, reductions in emulsion intake occurred at dosages that stimulated chow intake, again indicating that the rats did not suffer from any loss of motor function as a result of the drug administration. Baclofen's effect on simultaneously available chow in the present study (either no effect or a significant increase) is consistent with previous reports of baclofen's effects on chow intake (e.g., Brebner et al, 2000;Buda-Levin, et al, 2005;Ebenezer, 1995;Ebenezer and Pringle, 1992;Ebenezer and Patel, 2004;Higgs and Barber, 2004;Wojnicki, et al, 2006).…”

“…Previous work has shown that baclofen, a gamma-aminobutyric acid B (GABA B ) agonist, reduces intake of 100% vegetable shortening under limited access conditions. While baclofen was equally effective in "binge" and "non-binge" groups, the same study showed no effect of baclofen on intake of a continuously available fat-matched chow (∼15% fat by weight, or ∼30% fat by energy), suggesting the importance of the manner in which the fat is consumed and/or its concentration (Buda-Levin et al 2005). …”

“…The following drugs (Tocris, Ellisville, MO) were dissolved in saline and administered intraperitoneally (IP) in a volume of 1 ml/kg: the GABA B agonist (R-S)-baclofen (0.0 (vehicle), 0.6, 1.0, and 1.8 mg/kg, 30-min pretreatment), the D 2 -like antagonist raclopride (0.0 (vehicle), 0.03, 0.1, and 0.3 mg/kg, 20-min pretreatment), and the opioid antagonist naltrexone (0.0 (vehicle), 0.03, 0.1, and 0.3 mg/kg, 20-min pretreatment). These drugs and dosages were selected based upon previous reports of their effects on palatable food intake (Baker et al, 2001;Buda-Levin et al, 2005, Stein et al, 2000, as well as a recent report describing effects on binge-type consumption of 100% vegetable shortening (Corwin and Wojnicki, 2006).…”

“…In addition, the present study involved consumption of a large quantity of emulsion in a relatively short period of time (1 hour). Previous studies have shown the fat intake-reducing effects of baclofen occur under both the Daily and Intermittent access protocols, but not when fat is included in a fat-matched chow available 24 hours a day (Buda-Levin et al, 2005). Consequently, it is important to consider the quantity of fat consumed, as well as the manner in which it is consumed, when looking at the fat-specific effects of baclofen.…”

Positive Effect of Baclofen on Body Weight Reduction in Obese Subjects: A Pilot Study

“…Recent studies also reported that baclofen was effective to treat binge-eating of fat in animals (14) as well as binge-eating in humans (15), the mechanisms of which have been postulated to be similar to drug abuse (14). While we have not examined changes in the desire for fat exclusively, the desire to take sweets evaluated by a visual analogue scale was decreased by baclofen in this study.…”