Articles: nucleus-accumbens-drug-effects.
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The present studies aimed to determine whether cocaine- and amphetamine-regulated transcript (CART) peptide in the nucleus of accumbens shell (AcbSh) is implicated in the regulation of food intake. Bilateral intranuclear injections of CART peptide (55-102, 1 microg/microl/side) into the AcbSh decreased food intake with no change in locomotion activity and attenuated the orexigenic effect of the GABA(A) agonist muscimol (100 ng/microl/side) in male Sprague-Dawley rats. Decreased food intake after bilateral intranuclear injections of CART was more sustained in freely fed rats than in food-deprived rats, suggesting fuel availability is an important factor in modulating the function of CART in the regulation of feeding. ⋯ Moreover, many of these efferent cells contain CART immunoreactivity, including those which reside within the AcbSh, suggesting that accumbal CART circuitry is involved in the central function of the nucleus accumbens. Furthermore, fasting suppressed CART mRNA levels in the AcbSh, paraventricular nucleus of the hypothalamus, arcuate nucleus, and the perifornical region, indicating that the Acb is sensitive to fuel availability to an extent similar to those regions in the hypothalamus. Our findings are the first to demonstrate that CART mRNA in the AcbSh is sensitive to metabolic challenges and that injection of CART peptide into the AcbSh has an inhibitory effect on food intake.
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Most drugs of abuse increase dopamine (DA) in the nucleus accumbens (NAc), and do so every time as a pharmacological response. Palatable food also releases accumbens-shell DA, but in naïve rats the effect can wane during a long meal and disappears with repetition. Under select dietary circumstances, sugar can have effects similar to a drug of abuse. ⋯ In the Daily Intermittent Sucrose group, the highest ACh levels (133%) occurred during the first sample after the sucrose meal ended. In summary, sucrose-dependent animals have a delayed ACh satiation response, drink more sucrose, and release more DA than sucrose- or binge-experienced, but non-dependent animals. These results suggest another neurochemical similarity between intermittent bingeing on sucrose and drugs of abuse: both can repeatedly increase extracellular DA in the NAc shell.
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J. Pharmacol. Exp. Ther. · May 2004
Differential conditioned place preference responses to endomorphin-1 and endomorphin-2 microinjected into the posterior nucleus accumbens shell and ventral tegmental area in the rat.
An unbiased conditioned place preference (CPP) paradigm was used to evaluate the reward effects of endogenous mu-opioid receptor ligands endomorphin-1 (EM-1) and endomorphin-2 (EM-2) from the mesolimbic posterior nucleus accumbens (Acb) shell and the ventral tegmental area (VTA) in CD rats. EM-1 (1.6-8.1 nmol) microinjected into posterior Acb shell produced CPP, whereas EM-2 (8.7-17.5 nmol) given into the same Acb shell produced conditioned place aversion (CPA). EM-1 (1.6-16.3 nmol) microinjected into the VTA produced CPP, whereas EM-2 (8.7 and 17.5 nmol) given into the same VTA site did not produce any effect, but at a high dose (35 nmol) produced CPP. ⋯ Coadministration with antiserum against dynorphin A(1-17) (Dyn) (10 microg) microinjected into the posterior Acb shell blocked EM-2-induced CPA. However, it did not affect EM-1-induced CPP. It is concluded that EM-1 and EM-2 produce site-dependent CPP and CPA, respectively, by stimulation of different subtypes of mu-opioid-receptors; stimulation of one subtype of mu-opioid-receptor at the posterior Acb shell and VTA by EM-1 induces CPP, whereas stimulation of another subtype of mu-opioid receptor at the posterior Acb shell, but not the VTA, by EM-2 induces the release of Dyn to produce CPA.
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Neuropsychopharmacology · Feb 2004
Comparative StudyIn vivo evidence that 5-HT2C receptor antagonist but not agonist modulates cocaine-induced dopamine outflow in the rat nucleus accumbens and striatum.
During recent years, much attention has been devoted at investigating the modulatory role of central 5-HT(2C) receptors on dopamine (DA) neuron activity, and it has been proposed that these receptors modulate selectively DA exocytosis associated with increased firing of DA neurons. In the present study, using in vivo microdialysis in the nucleus accumbens (NAc) and the striatum of halothane-anesthetized rats, we addressed this hypothesis by assessing the ability of 5-HT(2C) agents to modulate the increase in DA outflow induced by haloperidol and cocaine, of which the effects on DA outflow are associated or not with an increase in DA neuron firing, respectively. The intraperitoneal administration of cocaine (10-30 mg/kg) induced a dose-dependent increase in DA extracellular levels in the NAc and the striatum. ⋯ The mixed 5-HT(2C/2B) agonist, Ro 60-0175 (1 mg/kg i.p.), failed to affect cocaine-induced DA outflow, but reduced significantly the increase in DA outflow induced by the subcutaneous administration of 0.1 mg/kg haloperidol. The obtained results provide evidence that 5-HT(2C) receptors exert similar effects in both the NAc and the striatum, and they modulate DA exocytosis also when its increase occurs independently from an increase in DA neuron impulse activity. Furthermore, they show that 5-HT(2C) agonists, at variance with 5-HT(2C) antagonists, exert a preferential control on the impulse-stimulated release of DA.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Nov 2003
Comparative StudyEffects of the opioid antagonist naltrexone on feeding induced by DAMGO in the ventral tegmental area and in the nucleus accumbens shell region in the rat.
The nucleus accumbens shell region (sNAcc) and the ventral tegmental area (VTA) are two major nodes in the mesolimbic dopamine pathway, which mediates reward for various survival behaviors, including feeding. Opioids increase and maintain food intake when injected peripherally and centrally. Opioids in the VTA cause increased release of dopamine in the sNAcc, and when injected into either site, cause an increase in food intake. ⋯ DAMGO was found to dose dependently increase intake to an equal extent when injected into either site. DAMGO-induced increases in food intake when injected into the VTA were blocked to control levels with the highest dose of NTX injected bilaterally into the sNAcc; however, increases in intake when injected into the sNAcc were blocked only partially by the highest dose of NTX injected bilaterally into the VTA. These results indicate opioid-opioid communication between the two sites; however, the communication may be quite indirect, requiring other sites and transmitters to elicit a change in behavior.