Cocaine cue–induced dopamine release in the human prefrontal cortex

Abstract

IntroductionThe prefrontal cortex (PFC) integrates and interprets sensory information, processing value, directing attention, and planning actions based on experience.1,2 In cocaine-dependent individuals, these regions and processes are engaged by drug-related cues, increasing the likelihood of craving and drug pursuit.3-5 For each of these effects, dopamine (DA) is a plausible contributing transmitter. Mesocortical DA transmission plays a critical role in cognitive and executive functions, 6 and, in laboratory animals, DA infusions into the PFC reinstate cocaine-seeking behaviours 7,8 while DA depletion or receptor antagonists reduce the drug's reinforcing efficacy. 9Based on these observations, it has been proposed that PFC abnormalities seen in cocaine-dependent individuals 10 are related at least in part to experience-dependent changes in DA transmission. 11,12 Dopamine release in the human PFC and striatum can be measured following an amphetamine challenge with positron emission tomography (PET) and the 18 F-labelled tracer fallypride. 13,14 More recently, the radioligand's PFC sensitivity to nonpharmacological manipulations of the DA system has also been demonstrated using psychological stressors.15-17 Here, we used [ 18 F]fallypride and high-resolution PET to assess the ability of drug-related cues to elicit DA release in the PFC of volunteers meeting criteria for current cocaine dependence. Given the role of DA in conditioned approach and incentive learning, 18 we hypothesized that exposure to familiar, drugrelated stimuli would enhance DA signalling in prefrontal and, in particular, orbitofrontal regions, contributing to the generation of motivational states that lead to drug seeking. 5,19Based on earlier reports identifying an association between PFC activation and self-reported craving, 3,20,21 a positive correlation between PFC DA release and craving was predicted. , 2015; Revised Sept. 9, 2015; Accepted Oct. 19, 2015; Early-released Feb. 23, 2016 DOI: 10.1503 Background: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. Methods: We used highresolution positron emission tomography with [

Is there a relation between novelty seeking, striatal dopamine release and frontal cortical thickness?

“…Decreased D 2 autoreceptor expression may be associated with greater amphetamine-induced DA release in the LS ( vs . other striatal regions) [28],[54], though the effect of fewer DATs is less clear [38],[55]. The LS also sends non-reciprocal GABAergic projections to the ASTS, as such, ASTS activity is regulated by LS GABAergic input (similarly, the ASTS appears to regulate the SMS via GABA projections) [38],[55].…”

Neurobiology of addiction: a neurocircuitry analysis

“…101–105 Imaging studies have also revealed that cues associated with cocaine craving increase dopamine release in the striatum, amygdala, and prefrontal cortex (anterior cingulate and medial orbitofrontal cortex) and opioid peptides in the anterior cingulate and frontal cortex. 9,31,106,107 Indeed, imaging studies have revealed baseline decreases in orbitofrontal (medial and lateral) and anterior cingulate (ventral and dorsal) function and dopamine function during dependence, but reactivation of dopamine and reward system function during acute craving episodes. 108 …”

‘Hot’ vs. ‘cold’ behavioural‐cognitive styles: motivational‐dopaminergic vs. cognitive‐cholinergic processing of a Pavlovian cocaine cue in sign‐ and goal‐tracking rats

“…This experiment was designed to measure the effects of presentation of a Pavlovian cue previously associated with IV injections of cocaine on the activity of two major neuromodulatory inputs to the prefrontal cortex, dopamine (DA) and ACh. We hypothesized that STs would express their preference for cue‐directed behaviour and that increases in cortical extracellular DA levels would be associated with their bias for processing of the motivational attributes of the cocaine cue, as has been described in cocaine addicts (Milella et al ., ). Furthermore, in STs, such cue‐evoked increases in prefrontal DA levels may stabilize such cue‐directed behaviour, even under extinction conditions (Ellwood et al ., ).…”