Mapping the Neural Substrates of Cocaine Craving: A Systematic Review

Abstract

Craving is one of the most important symptoms of cocaine use disorder (CUD) since it contributes to the relapse and persistence of such disorder. This systematic review aimed to investigate which brain regions are modulated during cocaine craving. The articles were obtained through searches in the Google Scholar, Regional BVS Portal, PubMed, and Scielo databases. Overall, there was a selection of 36 studies with 1574 individuals, the majority being participants with CUD, whereby about 61.56% were individuals with CUD and 38.44% were controls (mean age = 40.4 years). Besides the methodological points, the neurobiological investigations comprised fMRI (58.34%) and PET (38.89%). The induction of cocaine craving was studied using different methods: exposure to cocaine cues (69.45%), stressful stimuli, food cues, and methylphenidate. Brain activations demonstrated widespread activity across the frontal, parietal, temporal, and occipital lobes, basal ganglia, diencephalon, brainstem, and the limbic system. In addition to abnormalities in prefrontal cortex activity, abnormalities in various other brain regions' activity contribute to the elucidation of the neurobiology of cocaine craving. Abnormalities in brain activity are justified not only by the dysfunction of dopaminergic pathways but also of the glutamatergic and noradrenergic pathways, and distinct ways of inducing craving demonstrated the involvement of distinct brain circuits and regions.

Keywords: cocaine; craving; neurobiology; neuroimaging.

Figure 1

Identification of studies via databases and registers in accordance with the PRISMA 2020 flow diagram for new systematic reviews.

Figure 2

Brain activations in response to a myriad of stimuli, such as cocaine cues, stress, MP, monetary rewards, and cocaine itself. Brain activations in general correspond to the red and purple blocks. Brain activations of the limbic system correspond to the purple blocks. The limbic system is highlighted due to its importance in substance use disorders in general. The laterality of the brain activations corresponds to the blue and green blocks [7,11,12,13,15,16,17,18,21,25,26,29,32,34,35,38,40,42,43].

Figure 2

Brain activations in response to a myriad of stimuli, such as cocaine cues, stress, MP, monetary rewards, and cocaine itself. Brain activations in general correspond to the red and purple blocks. Brain activations of the limbic system correspond to the purple blocks. The limbic system is highlighted due to its importance in substance use disorders in general. The laterality of the brain activations corresponds to the blue and green blocks [7,11,12,13,15,16,17,18,21,25,26,29,32,34,35,38,40,42,43].

Figure 2

Brain activations in response to a myriad of stimuli, such as cocaine cues, stress, MP, monetary rewards, and cocaine itself. Brain activations in general correspond to the red and purple blocks. Brain activations of the limbic system correspond to the purple blocks. The limbic system is highlighted due to its importance in substance use disorders in general. The laterality of the brain activations corresponds to the blue and green blocks [7,11,12,13,15,16,17,18,21,25,26,29,32,34,35,38,40,42,43].

Figure 3

Brain activations of the limbic system in response to a myriad of stimuli, such as cocaine cues, stress, MP, monetary rewards, and cocaine itself, correspond to the purple blocks. The limbic system is highlighted due to its importance in substance use disorders in general. The laterality of the brain activations corresponds to the blue and green blocks [7,11,12,15,16,17,21,25,26,29,32,34,40,42,43,44,45].