Conditioned saccharin avoidance induced by infusion of amphetamine in the nucleus accumbens shell and morphine in the ventral tegmental area: behavioral and biochemical study.
Drugs of abuse possess the seemingly paradoxical property of conditioning rats to avoid from drinking a saccharin solution that had been predictively paired with their systemic administration (conditioned saccharin avoidance, CSA). CSA is dependent upon an intact dopamine (DA) transmission but the locus, central or peripheral, and eventually the brain area from which this effect originates and its relationship with the rewarding properties of the drug is debated. In order to clarify this issue we tested the ability of amphetamine and morphine to induce CSA after infusion at the same dose-range and in the same areas from which these drugs induce conditioned place preference (CPP). Drugs were infused intracerebrally immediately after saccharin drinking in two acquisition trials and CSA was tested on a two bottle saccharin/water choice. Amphetamine (10 and 20 μg/0.5 μl) induced CSA after infusion in the NAc shell but was ineffective in the NAc core. Morphine (0.5 and 1 μg/0.5 μl) induced CSA from the VTA at both doses tested. Amphetamine (20 μg/0.5 μl) and morphine (1 μg/0.5 μl) failed to induce CSA after infusion 1.2mm dorsal the NAc shell and the VTA respectively. Finally, morphine (1 μg/0.5 μl), infused in the VTA, elicited a selective increase in dialysate DA in the NAc shell. These results indicate that drugs of abuse induce CSA from the same intracerebral sites and at the same doses at which they induce CPP. These observations are consistent with the existence of a strong relationship between CSA and drug reward related to their ability to stimulate DA transmission in the NAc shell.
Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy; INN - National Institute of Neuroscience, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy; Center of Excellence for the Neurobiology of Dependence, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy. Electronic address: sfenu@unica.it.
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Fenu
Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
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Espa
INN - National Institute of Neuroscience, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy; Center of Excellence for the Neurobiology of Dependence, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy; National Research Council of Italy, Neuroscience Institute, Cagliari Section, Cagliari, Italy.
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Cadoni
Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy; INN - National Institute of Neuroscience, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy; Center of Excellence for the Neurobiology of Dependence, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy; National Research Council of Italy, Neuroscience Institute, Cagliari Section, Cagliari, Italy. Electronic address: gadichia@tiscali.it.
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Di Chiara
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000502:physiology; D013287:Illicit Drugs / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D012439:Saccharin / Q000008:administration & dosage; D013028:Space Perception / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
D015259:Dopamine Agents; D013287:Illicit Drugs; D009294:Narcotics; D009020:Morphine; D000661:Amphetamine; D012439:Saccharin; D004298:Dopamine
Conditioned saccharin avoidance; Dopamine; Nucleus accumbens core; Nucleus accumbens shell; Reward; Ventral tegmental area