Adenosine A2a receptors in the nucleus accumbens mediate locomotor depression

Barraco, Robin A.; Martens, Kevin; Parizon, M.; Normile, Howard J.

doi:10.1016/0361-9230(93)90233-2

Cited by 116 publications

(68 citation statements)

References 30 publications

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“…Consistent with these previous findings of an interaction between DA and adenosine receptors, adenosine A 2A agonists have been shown to induce effects that resemble those produced by DA antagonists or DA depletions (Heffner et al 1989;Barraco et al 1993;Ferré 1997;Rimondini et al 1997). Administration of the adenosine A 2A receptor agonist CGS 21680 into the ventricles inhibited acquisition and expression of wheel running behavior (Cabeza de Vaca et al 2007).…”

Section: Introductionsupporting

confidence: 84%

“…High systemic doses of CGS 21680 have been shown to induce catalepsy (Wardas et al 2003). In addition, CGS 21680 depressed locomotor activity when infused directly into the nucleus accumbens (Barraco et al 1993;Hauber and Munkel 1997). Although it seems clear that stimulation of adenosine A 2A receptors in nucleus accumbens can suppress locomotor activity, relatively little is known about the role of these receptors in the regulation of effortrelated processes.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionsupporting

confidence: 84%

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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“…For example, intraventricular administration of the adenosine A 2A receptor agonist CGS 21680 inhibited acquisition and expression of wheel running behavior (Cabeza de Vaca et al, 2007). CGS 21680 depressed locomotor activity when infused directly into the nucleus accumbens (Barraco et al, 1993;Hauber and Munkel, 1997). Stimulation of adenosine A 2A receptors with high doses of CGS 21680 also was shown to induce catalepsy (Wardas et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

Mingote

Pereira

Farrar

et al. 2008

Pharmacology Biochemistry and Behavior

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Adenosine A 2A receptors are involved in the regulation of several behavioral functions. Adenosine A 2A antagonists exert antiparkinsonian effects in animal models, and adenosine A 2A agonists suppress locomotion and impair various aspects of motor control. The present experiments were conducted to study the effects of low doses of the adenosine A 2A agonist CGS 21680 on lever pressing, specific parameters of food intake, and sedation. In the first experiment, the effects of CGS 21680 on fixed ratio 5 lever pressing were assessed. In the second experiment, rats were tested in 30 min feeding sessions, and also were observed for drug-induced sedation using a sedation rating scale. CGS 21680 (0.025, 0.05, 0.1 mg/kg IP) produced a dose related suppression of lever pressing, and also reduced the amount of food consumed. The feeding effect was largely dependent upon a slowing of the rate of feeding, and there was only a modest suppression of time spent feeding. Doses of CGS 21680 that suppressed lever pressing and feeding also were associated with sedation/drowsiness. In conjunction with other studies, the present results suggest that sedative effects may play an important role in some of the behavioral effects produced by systemic administration of adenosine A 2A agonists.

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“…Adenosine, by acting on both A 1 and A 2A receptors, is implicated in the regulation of motor activity. There is clear experimental evidence for a central mediation of the motor-depressant effects of A 1 and A 2A receptor agonists (Snyder et al, 1981;Katz and Goldberg, 1987;Nikodijevic et al, 1990;Barraco et al, 1993;Marston et al, 1998), independent of their pronounced cardiovascular effects (Appel et al, 1995;Mathot et al, 1995). In contrast, some contradictory results exist regarding the motor-activating effects of adenosine antagonists and there is no consensus about the relative involvement of A 1 and A 2A receptors in caffeine-induced motor activation.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Adenosine A1 and A2A Receptors in the Motor Effects of Caffeine after its Acute and Chronic Administration

Karcz-Kubicha¹,

Αντωνίου²,

Terasmaa

et al. 2003

Neuropsychopharmacol

180

189

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The involvement of adenosine A 1 and A 2A receptors in the motor effects of caffeine is still a matter of debate. In the present study, counteraction of the motor-depressant effects of the selective A 1 receptor agonist CPA and the A 2A receptor agonist CGS 21680 by caffeine, the selective A 1 receptor antagonist CPT, and the A 2A receptor antagonist MSX-3 was compared. CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by CPA and CGS 21680, respectively. Caffeine also counteracted motor depression induced by CPA and CGS 21680 at doses that produced motor activation. However, caffeine was less effective than CPT at counteracting CPA and even less effective than MSX-3 at counteracting CGS 21680. On the other hand, when administered alone in habituated animals, caffeine produced stronger motor activation than CPT or MSX-3. An additive effect on motor activation was obtained when CPT and MSX-3 were coadministered. Altogether, these results suggest that the motoractivating effects of acutely administered caffeine in rats involve the central blockade of both A 1 and A 2A receptors. Chronic exposure to caffeine in the drinking water (1.0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true crosstolerance to CPT. The present results suggest that development of tolerance to the effects of A 1 receptor blockade might be mostly responsible for the tolerance to the motor-activating effects of caffeine and that the residual motor-activating effects of caffeine in tolerant individuals might be mostly because of A 2A receptor blockade.

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Adenosine A2a receptors in the nucleus accumbens mediate locomotor depression

Cited by 116 publications

References 30 publications

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

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

Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

Involvement of Adenosine A1 and A2A Receptors in the Motor Effects of Caffeine after its Acute and Chronic Administration

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