Accumbens dopamine and the regulation of effort in food-seeking behavior: modulation of work output by different ratio or force requirements

Ishiwari, Keita; Weber, Suzanne M.; Mingote, Susana; Correa, Mercè; Salamone, John D.

doi:10.1016/j.bbr.2003.08.007

Cited by 114 publications

(106 citation statements)

References 42 publications

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…This result was somewhat of a surprise, as it was thought that a neutral antagonist blocking endogenous tone would be equipotent across both ratio schedules, similar to the effects of prefeeding (Aberman and Salamone, 1999). Furthermore, this result was quite different from previous studies involving dopaminergic manipulations, which have demonstrated that schedules with higher ratio requirements are much more sensitive to the effects of interference with DA transmission (Aberman and Salamone, 1999;Ishiwari et al, 2004). Interestingly, CB1 agonists also produce decreases in FR5 responding; however, it is thought that the mechanisms causing these response reductions are quite different from those of CB1 antagonists.…”

Section: Discussionmentioning

confidence: 73%

“…Moreover, research on the effects of other manipulations (eg nucleus accumbens dopamine depletions, dopamine antagonists) has indicated that the ratio requirement of a schedule can be a critical determinant of the effects of various neurochemical or pharmacological manipulations (Aberman and Salamone, 1999;Ishiwari et al, 2004). In the present study, AM4113 decreased responding on the FR1 schedule with an ED 50 of 4.78 mg/kg; however, the potency of AM4113 for suppression of FR5 responding was somewhat less (ie 10.28 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Novel Cannabinoid CB1 Receptor Neutral Antagonist AM4113 Suppresses Food Intake and Food-Reinforced Behavior but Does not Induce Signs of Nausea in Rats

Sink

McLaughlin

Wood

et al. 2007

Neuropsychopharmacol

143

193

View full text Add to dashboard Cite

Drugs that interfere with cannabinoid CB1 transmission suppress various food-motivated behaviors, and it has been suggested that such drugs could be useful as appetite suppressants. Biochemical studies indicate that most of these drugs assessed thus far have been CB1 inverse agonists, and although they have been shown to suppress food intake, they also appear to induce nausea and malaise. The present studies were undertaken to characterize the behavioral effects of AM4113, which is a CB1 neutral antagonist, and to examine whether this drug can reduce food-reinforced behaviors and feeding on diets with varying macronutrient compositions. Biochemical data demonstrated that AM4113 binds to CB1 receptors, but does not show inverse agonist properties (ie no effects on cyclic-AMP production). In tests of spontaneous locomotion and analgesia, AM4113 reversed the effects of the CB1 agonist AM411. AM4113 suppressed food-reinforced operant responding with rats responding on fixed ratio (FR) 1 and 5 schedules of reinforcement in a dosedependent manner, and also suppressed feeding on high-fat, high-carbohydrate, and lab chow diets. However, in the same dose range that suppressed feeding, AM4113 did not induce conditioned gaping, which is a sign of nausea and food-related malaise in rats. These results suggest that AM4113 may decrease appetite by blocking endogenous cannabinoid tone, and that this drug may be less associated with nausea than CB1 inverse agonists. Neuropsychopharmacology (2008) 33, 946-955;

show abstract

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

The Novel Cannabinoid CB1 Receptor Neutral Antagonist AM4113 Suppresses Food Intake and Food-Reinforced Behavior but Does not Induce Signs of Nausea in Rats

Sink

McLaughlin

Wood

et al. 2007

Neuropsychopharmacol

143

193

View full text Add to dashboard Cite

show abstract

“…In the progressive ratio task utilizing natural reward, dopamine antagonists only reduce operant responding on the active lever, not the inactive one, and only when animals are food deprived (Aberman et al, 1998;Hamill et al, 1999). In the concurrent food choice task, a similar reduction in responding is only seen in the 'choice' condition, not the 'no choice' condition Cousins et al, , 1996Salamone et al, 1995Salamone et al, , 2001Salamone et al, , 2002Sokolowski and Salamone, 1998;Aberman and Salamone, 1999;Nowend et al, 2001;Correa et al, 2002;Ishiwari et al, 2004;Mingote et al, 2005), suggesting that the role of dopamine becomes important when the task requires the ability to increase effort. Similarly, previous work in our laboratory utilizing genetic repression of dopamine transporter (DAT) expression (which elevates extracellular dopamine levels) has demonstrated increased operant responding for food reward in the progressive ratio task only on the active lever and only when food-deprived (Cagniard et al, 2006).…”

Section: -Ht Reduces Operant Responding For Reward Ac Sanders Et Almentioning

confidence: 99%

Chronic Blockade or Constitutive Deletion of the Serotonin Transporter Reduces Operant Responding for Food Reward

Sanders

Hussain

Hen

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

The therapeutic effects of chronic selective serotonin reuptake inhibitors (SSRIs) are well documented, yet the elementary behavioral processes that are affected by such treatment have not been fully investigated. We report here the effects of chronic fluoxetine treatment and genetic deletion of the serotonin transporter (SERT) on food reinforced behavior in three paradigms: the progressive ratio operant task, the concurrent choice operant task, and the Pavlovian-to-Instrumental transfer task. We consistently find that chronic pharmacological blockade or genetic deletion of SERT result in similar behavioral consequences: reduced operant responding for natural reward. This is in line with previous studies reporting declines in operant responding for drugs and intracranial self-stimulation with fluoxetine treatment, suggesting that the effect of SERT blockade can be generalized to different reward types. Detailed analyses of behavioral parameters indicate that this reduction in operant responding affect both goal-directed and non-goal-directed behaviors without affecting the Pavlovian cue-triggered excessive operant responding. In addition, both pharmacological and genetic manipulations reduce locomotor activity in the open field novel environment. Our data contrast with the effect of dopamine in increasing operant responding for natural reward specifically in goal-directed behaviors and in increasing Pavlovian cue-triggered excessive operant responding. Serotonin and dopamine have been proposed to serve opposing functions in motivational processes. Our data suggest that their interactions do not result in simple opponency. The fact that pharmacological blockade and genetic deletion of SERT have similar behavioral consequences reinforces the utility of the SERT null mice for investigation of the mechanisms underlying chronic SSRIs treatment.

show abstract

“…Furthermore, Ob rats show a distinct DA profile that responds uniquely to fasting and food restriction (Michaelides et al, 2006;Thanos et al, 2007). Therefore, differences in DA and its receptors between Ob and Le rats may also contribute to the operant FSA behavior observed, especially since pharmacological manipulation of DA and D 2 receptors has been shown to modulate food operant responding (Barrett et al, 2004;Ishiwari et al, 2004). Future experiments measuring D 3 receptor levels in Ob and Le Zucker rats may shed light on the involvement of D 3 receptors in weight gain and food intake and how these responses may be modulated by leptin.…”

Section: Zucker Ob Rats and Fsamentioning

confidence: 99%

The effects of two highly selective dopamine D3 receptor antagonists (SB-277011A and NGB-2904) on food self-administration in a rodent model of obesity

Thanos

Michaelides

et al. 2008

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

In the current study, we examined the effect of the selective D 3 receptor antagonists SB-277011A and NGB 2904 on operant food self-administration (FSA) in Zucker obese and lean rats. Obese (Ob) and lean (Le) Zucker rats were maintained under a restricted feeding regimen (70% of ad-libitum rat chow) and were trained to lever press for food during daily, 2 hour fixed-ratio 4 (FR4) schedules. Once rats reached a stable baseline for FSA, they were injected with vehicle until a stable FSA criterion was achieved. Animals then received daily injections of different random doses of SB-277011A (3, 10, and 30 mg/kg i.p.), and NGB-2904 (0.3, 1 and 3 mg/kg i.p.). SB-277011A produced a significant decrease in both food intake and active lever responses in both Ob and Le rats. In contrast, NGB-2904 did not decrease food intake levels or lever presses for food in Ob and Le rats. These results suggest that along with its involvement in seeking behavior for drugs of abuse, the D 3 dopamine receptor may also be involved in seeking behavior for natural reinforcers such as food.

show abstract

Accumbens dopamine and the regulation of effort in food-seeking behavior: modulation of work output by different ratio or force requirements

Cited by 114 publications

References 42 publications

The Novel Cannabinoid CB1 Receptor Neutral Antagonist AM4113 Suppresses Food Intake and Food-Reinforced Behavior but Does not Induce Signs of Nausea in Rats

The Novel Cannabinoid CB1 Receptor Neutral Antagonist AM4113 Suppresses Food Intake and Food-Reinforced Behavior but Does not Induce Signs of Nausea in Rats

Chronic Blockade or Constitutive Deletion of the Serotonin Transporter Reduces Operant Responding for Food Reward

The effects of two highly selective dopamine D3 receptor antagonists (SB-277011A and NGB-2904) on food self-administration in a rodent model of obesity

Contact Info

Product

Resources

About