Baclofen, raclopride, and naltrexone differentially affect intake of fat and sucrose under limited access conditions

Abstract

Gamma-aminobutyric acid (GABA), dopamine, and opioids are implicated in impulse control, addiction and binge eating. Recent evidence suggests that sucrose alters the effects of GABAergic, dopaminergic, and opioid receptor ligands on consumption of a fatty food in a rat limited-access binge protocol. This study determined the independent effects of fat and sucrose on the efficacy of these ligands under limited-access conditions. Nonfood-deprived male Sprague-Dawley rats had 1 h access to fat (vegetable shortening) or sucrose (3.2, 10, or 32% w/v). Half had intermittent access (Monday, Wednesday, Friday) and half had daily access. Effects of baclofen (GABAB agonist), SCH 23390 (D1 antagonist), raclopride (D2 antagonist), and naltrexone (opioid antagonist) were assessed. Baclofen and naltrexone reduced fat intake regardless of the access schedule. Baclofen had no effect on sucrose intake; naltrexone reduced sucrose intake at higher doses than were required to reduce fat intake. Raclopride stimulated fat intake in intermittent-access rats and had no effect in daily-access rats; raclopride reduced sucrose intake in all groups. SCH 23390 reduced intake in a nonspecific manner. The results indicate the involvement of GABAB receptors in fat but not sucrose intake, and of D2 receptor dysfunction in rats with a history of bingeing on fat.

Operant, oral alcoholic beer self-administration by C57BL/6J mice: effect of BHF177, a positive allosteric modulator of GABAB receptors

“…The lack of selectivity in the present study is consistent with baclofen's reported ability to alter seeking behavior and consumption of several reinforcers such as normal chow (Ebenezer, 1995), fatty food (Corwin and Wojnicki, 2009), cocaine (Roberts et al, 1996), heroin (Xi and Stein, 1999) and nicotine (Corrigall et al, 2001). Moreover, doses higher than 5 mg/kg can induce sedation in mice (Besheer et al, 2004;Cryan et al, 2004).…”

Rodent Models of Binge Eating: Are They Models of Addiction?

“…Avena and colleagues (2009), for instance, reported withdrawallike symptoms in rats bingeing on sugar solutions, but not in rats bingeing on pure fat or fatty foods. In addition, our group has shown that opioid blockade more potently reduced sucrose intake in bingeing rats than in controls; potency differences were not seen in rats consuming fat (Corwin and Wojnicki 2009). These results suggest a unique role for endogenous opioids in sugar bingeing but not in fat bingeing.…”

“…We previously reported effects of various peripherally administered pharmacological probes in rats bingeing on sugar solutions and solid fats (Corwin and Wojnicki 2009). Results from these studies indicate differential involvement of dopamine D 2 -like receptors between INT and D rats consuming solid fats but not in INT and D rats consuming sugar solutions.…”

“…Finally, the Hoebel and Corwin labs have both reported differential effects of baclofen in rats bingeing on sugar or fat (Berner et al 2009;Corwin and Wojnicki 2009). Specifically, baclofen reduced solid fat intake in fat-bingeing rats but had no effect on liquid sugar intake in sugar-bingeing rats.…”

Food and Addiction – Sugars, Fats and Hedonic Overeating

“…Further, preclinical studies suggest that overeating sugar produces different addiction-like behaviors compared with overeating fat [5]. There is also a nutrient specificity in the effect that some pharmacological treatments have on reducing overeating [16,17]. Thus, additional knowledge of how different food elements activate brain systems that affect addiction-like behavior will be crucial to developing targeted interventions for people who exhibit signs of 'food addiction'.…”