Research reportConditioned saccharin avoidance induced by infusion of amphetamine in the nucleus accumbens shell and morphine in the ventral tegmental area: Behavioral and biochemical study

•Intra-NAc shell amphetamine and intra-VTA morphine induced CSA at doses known to induce CPP.•Intra-VTA morphine increases DA selectively in the NAc shell.•Drug-CSA is related to stimulation of DA transmission in the NAc shell.•Our results are consistent with a role of drug reward in morphine and amphetamine CSA.

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 1.2 mm 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.