The effects of the high-affinity dopamine reuptake inhibitor, GBR 12909, were studied on responding maintained under multiple fixed ratio schedules of food and cocaine delivery in rhesus monkeys (Macaca mulatta).
GBR 12909 decreased rates of responding maintained by both events in a dose-related manner, however large decreases in cocaine-maintained responding could be obtained with doses of GBR 12909 that had little effect on food-maintained responding. This behaviorally selective effect of GBR 12909 on cocaine-maintained responding was inversely related to the unit dose of cocaine. When responding was maintained by low doses of cocaine, GBR 12909 (1 mg/kg) decreased cocaine-maintained responding almost completely. When responding was maintained by the highest dose, the same dose of GBR 12909 had little effect on responding. To the extent that higher doses of cocaine may be expected to be more reinforcing, the current results suggest that the effect of GBR 12909 on cocaine-maintained responding was determined by the reinforcing efficacy of the unit dose of cocaine.
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.
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.
A previous study (J.R. Glowa, F.H.E. showed that acute doses of GBR 12909 selectively decreased cocaine-maintained responding without affecting foodmaintained responding. This report extended these observations to some related drugs and to the effects of repeated administration. When responding was maintained under a multiple fixed ratio (FR) 30 food, FR 30 cocaine schedule, acute doses of GBR 12935, CFT, and d-amphetamine decreased cocaine-maintained responding more than food-maintained responding. However, in contrast to GBR 12909, none of these drugs completely decreased cocaine-maintained responding without affecting food-maintained responding. Repeated administration of GBR 12909 sustained, and of GBR 12935 improved, these selective decreases in cocaine-maintained responding. The selective effect of these dopamine reuptake inhibitors on cocaine-maintained responding is consistent with their known pharmacological selectivity for the dopamine reuptake site and can be well-maintained with repeated administration.Glowa, found that the high-affinity dopamine (DA) reuptake inhibitor, GBR 12909, could decrease responding maintained by cocaine at doses that did not have effects on comparable rates of food-maintained responding. Similar results have been reported for other drugs. For example, Mello, Mendelson, Bree, & Lucas (1989) reported that the opioid buprenorphine suppressed cocaine self-administration in rhesus monkeys at doses that had little effect on food-maintained responding. These types of effects are of interest because few studies have reported comparable differences in the effects of other drugs on food-and drugmaintained responding. To the extent that it would be desirable for a treatment drug to selectively decrease cocaineseeking behavior, this type of effect may be useful in identifying therapeutic agents comparable to those used for heroin (e.g., methadone) or nicotine (e.g., nicotine patches) abuse. In
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