Dopamine mediates a variety of behaviors and functions, including selective attention, learning, motor functioning, hormone release, and goal-directed motivated behaviors [
121]. In this context, dopamine primarily encodes the incentive value (or the ‘wanting’) of reward. It is released in response to contextual cues predictive of reward, initiating a phase of reward anticipation and approach. Animal research shows that dopamine antagonists or agonists injected into the VTA and VS impair or facilitate, respectively, reward approach behaviors, but not reward consumption [
119]. In humans, drug-induced activity in the VS is linked to feelings of craving and ‘wanting’, but not to feelings of euphoria or pleasure [
122].
Dysfunction in the dopamine system in ASD has been suggested, based on the beneficial effects of dopamine receptor antagonists (for example, antipsychotic drugs such as risperidone) in treating certain symptoms commonly exhibited by affected individuals, such as stereotypies, aggression, hyperactivity, and self-injury [
123]. Because such symptoms can be induced in animals by increasing the dopamine level, it has been inferred that ASD might be associated with mesocorticolimbic dopaminergic overactivity. However, conflicting results have been found in studies measuring peripheral (for example, blood, urine) or central (for example, cerebrospinal fluid (CSF)) levels of dopamine and its metabolites, with some studies reporting atypical dopamine turnover in patients [
121]. Evidence is also scarce and inconclusive with regard to dopamine-related neuroimaging using positron emission tomography (PET) or single photon emission computed tomography (SPECT) in individuals with ASD. For instance, Ernst and colleagues [
124] found reduced dopamine metabolism in the vmPFC, but not in the VS, in children with ASD compared with controls. However, follow-up studies could not confirm this early finding, and reported either enhanced dopamine bindings in the vmPFC [
125], in the VS [
126,
127], or in both brain areas [
128], or did not find any abnormalities in ASD [
129]. It should be noted that urine, blood, CSF and baseline PET/SPECT measurements usually assess stable, tonic dopamine levels, whereas the beneficial effects of antipsychotic drugs stem from blocking phasic dopamine release, which only minimally contributes to these tonic levels [
130]. This raises the possibility of a dysfunction in the phasic rather than the tonic dopamine metabolism in ASD, which would be more consistent with the neuroimaging and electrophysiological findings of atypical reward ‘wanting’. Indeed, reward-predicting signals and behaviorally important events (for example, novel stimuli) elicit brief, phasic, bursts of dopamine impulses, which last less than 500 ms, and prompt reward anticipation [
12]. Research provides evidence that specific subpopulations of dopaminergic cells within the VS respond differently depending on reinforcer type. It has been shown that some striatal cell groups encode primary reinforcers (for example, water, food, sexual intercourse), whereas others are thought to be ‘idle’ and modifiable through reward-based learning (for example, drug conditioning [
131]). The idea that dopaminergic cell activity tracks different reward types is intriguing, because it might offer a simplistic, although plausible, explanation as to why some incentives (for example, objects of circumscribed interest) induce goal-directed approach behavior in individuals with ASD, whereas others (for example, social reward) do not. Such ‘selective’ impairment could be thought of as genetically driven [
132,
133], or acquired through aberrant learning experiences, or both. Because single-cell recordings are mostly limited to animal research, the use of mouse models of ASD could be a fruitful approach to test the merits of this idea [
134].