Nucleus accumbens dopamine depletions make rats more sensitive to high ratio requirements but do not impair primary food reinforcement

Aberman, J.; Salamone, John D.

doi:10.1016/s0306-4522(99)00004-4

Cited by 242 publications

(263 citation statements)

References 35 publications

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“…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). 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).…”

Section: Discussionmentioning

confidence: 69%

“…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: 94%

“…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%

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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

144

193

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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;

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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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

144

193

View full text Add to dashboard Cite

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“…Over the past two decades, considerable research has demonstrated that nucleus accumbens DA is a critical component of the brain circuitry controlling effort-related behavioral processes (Salamone et al , 1997Phillips et al 2007;Niv et al 2007). Depletions of DA in nucleus accumbens make animals highly sensitive to ratio requirements in operant schedules (Sokolowski and Salamone 1998;Aberman and Salamone 1999;Correa et al 2002;Mingote et al 2005). Furthermore, studies involving choice behavior have shown that rats administered DA receptor antagonists or rats with accumbens DA depletions reallocate their behavior away from food-reinforced tasks that have high response requirements and instead select less-effortful types of foodseeking behavior (Salamone et al , 1997(Salamone et al , 2003.…”

Section: Introductionmentioning

confidence: 99%

Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

et al. 2008

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Rationale-Nucleus accumbens dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired accumbens DA transmission reallocate their behavior away from food-reinforced activities that have high response requirements and instead select less-effortful types of food-seeking behavior. Although accumbens DA is considered a critical component of the brain circuitry regulating effortrelated processes, emerging evidence also implicates adenosine A 2A receptors.Objective-The present work was undertaken to test the hypothesis that accumbens A 2A receptor stimulation would produce effects similar to those produced by DA depletion or antagonism.Materials and methods-Three experiments assessed the effects of the adenosine A 2A agonist CGS 21680 on performance of a concurrent choice task (lever pressing for preferred food vs. intake of less preferred chow) that is known to be sensitive to DA antagonists and accumbens DA depletions.Results-Systemic injections of CGS 21680 reduced lever pressing but did not increase feeding. In contrast, bilateral infusions of the adenosine A 2A receptor agonist CGS 21680 (6.0-24.0 ng) into the nucleus accumbens decreased lever pressing for the preferred food but substantially increased consumption of the less preferred chow. Injections of CGS 21680 into a control site dorsal to the accumbens were ineffective.Conclusions-Taken together, these results are consistent with the hypothesis that local stimulation of adenosine A 2A receptors in nucleus accumbens produces behavioral effects similar to those induced by accumbens DA depletions. Accumbens adenosine A 2A receptors appear to be a component of the brain circuitry regulating effort-related choice behavior.

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“…Pharmacological and genetic blockade of dopamine receptors has been shown to reduce operant responding for food (Hoffman and Beninger, 1989;Nakajima, 1989), to disrupt instrumental responses in a sucrose-reinforced runway task (Ikemoto and Panksepp, 1996), and an appetitive T-maze task (Robinson et al, 2005). Interestingly, dopaminergic lesion of the nucleus accumbens reduced lever pressing for food under a high workload (fixed ratio (FR) 16 and FR64) but not under a low workload (FR1) condition (Aberman and Salamone, 1999;McCullough et al, 1993). Similarly, in a T-maze experiment, blockade of dopamine receptors or depletion of accumbens dopamine induced a shift from climbing a barrier to access an arm with high density of reward, to enter an unobstructed arm with a low density of reward (Cousins et al, 1996;Salamone et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Mice with Chronically Elevated Dopamine Exhibit Enhanced Motivation, but not Learning, for a Food Reward

Cagniard

Balsam

Brunner

et al. 2005

Neuropsychopharmacol

236

158

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Dopamine has been critically implicated in learning and motivation, although its precise role remains to be determined. In order to investigate the involvement of dopamine in learning and motivation for a food reward, we used dopamine transporter knockdown mice (DAT KD) that have chronically elevated levels of extracellular dopamine. The present study demonstrates that chronically elevated dopamine enhances tendency to work for a food reward without apparent effects on Pavlovian and operant learning for this reward. The increase in dopamine is associated with elevated levels of dynorphin and Fos B expression in the dorsal caudate-putamen and the core but not the shell subregion of the nucleus accumbens. These data suggest that motivation to work, but not learning, for a food reward appears to be under the critical influence of tonic dopaminergic activity in discrete brain areas relevant for a reward-directed behavior.

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Nucleus accumbens dopamine depletions make rats more sensitive to high ratio requirements but do not impair primary food reinforcement

Cited by 242 publications

References 35 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

Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

Mice with Chronically Elevated Dopamine Exhibit Enhanced Motivation, but not Learning, for a Food Reward

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