Dissociation of dopamine release in the nucleus accumbens from intracranial self-stimulation

Mesolimbic dopamine-releasing neurons appear to be important in the brain reward system1,2. One behavioural paradigm that supports this hypothesis is intracranial self-stimulation (ICS), during which animals repeatedly press a lever to stimulate their own dopamine-releasing neurons electrically3,4,5,6. Here we study dopamine release from dopamine terminals in the nucleus accumbens core and shell in the brain by using rapid-responding voltammetric microsensors7 during electrical stimulation of dopamine cell bodies in the ventral tegmental area/substantia nigra brain regions. In rats in which stimulating electrode placement failed to elicit dopamine release in the nucleus accumbens, ICS behaviour was not learned. In contrast, ICS was acquired when stimulus trains evoked extracellular dopamine in either the core or the shell of the nucleus accumbens. In animals that could learn ICS, experimenter-delivered stimulation always elicited dopamine release. In contrast, extracellular dopamine was rarely observed during ICS itself. Thus, although activation of mesolimbic dopamine-releasing neurons seems to be a necessary condition for ICS, evoked dopamine release is actually diminished during ICS. Dopamine may therefore be a neural substrate for novelty8 or reward expectation9 rather than reward itself.