Cue-elicited functional connectivity of the periaqueductal gray and tonic cocaine craving

Zhang, Sheng; Zhornitsky, Simon; Wang, Wuyi; Dhingra, Isha; Le, Thang M.; Li, Chiang‐Shan R.

doi:10.1016/j.drugalcdep.2020.108240

Cited by 13 publications

(32 citation statements)

References 81 publications

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“…In addition to common brain regions impacted by SUD, recent findings reported changes in periaqueductal gray (PAG) connectivity in CUD. Cocaine craving was positively correlated with PAG-ventromedial prefrontal cortex (vmPFC) connectivity in males, yet the reverse was true for females ( 49 ), however noting that healthy controls were not compared to in this study. There are other brain regions involved in SUD such as the subthalamic nucleus ( 50 ) and ventral subiculum ( 51 , 52 ), that are yet to be investigated with respect to sex dependent analysis.…”

Section: Perspectivesmentioning

confidence: 65%

Sex Differences in Substance Use Disorders: A Neurobiological Perspective

Cornish

Prasad

2021

Front. Glob. Womens Health

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Clinical studies provide fundamental knowledge of substance use behaviors (substance of abuse, patterns of use, relapse rates). The combination of neuroimaging approaches reveal correlation between substance use disorder (SUD) and changes in neural structure, function, and neurotransmission. Here, we review these advances, placing special emphasis on sex specific findings from structural neuroimaging studies of those dependent on alcohol, nicotine, cannabis, psychostimulants, or opioids. Recent clinical studies in SUD analyzing sex differences reveal neurobiological changes that are differentially impacted in common reward processing regions such as the striatum, hippocampus, amygdala, insula, and corpus collosum. We reflect on the contribution of sex hormones, period of drug use and abstinence, and the potential impact of these factors on the interpretation of the reported findings. With the overall recognition that SUD impacts the brains of females and males differentially, it is of fundamental importance that future research is designed with sex as a variable of study in this field. Improved understanding of neurobiological changes in males and females in SUD will advance knowledge underlying sex-specific susceptibility and the neurobiological impact in these disorders. Together these findings will inform future treatments that are tailor designed for improved efficacy in females and males with SUD.

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Section: Perspectivesmentioning

confidence: 65%

Sex Differences in Substance Use Disorders: A Neurobiological Perspective

Cornish

Prasad

2021

Front. Glob. Womens Health

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“…Brain activity changes induced by cocaine or stress cues were compared to those induced by neutral cues. Participants in these studies were either abstinent and underwent inpatient or outpatient treatment 43,181,182 or were non-treatment seeking active cocaine users 38 .…”

Section: Discussionmentioning

confidence: 99%

“…Zhang et al 182 used fMRI to investigate periaqueductal gray (PAG) activity and connectivity between PAG and ventromedial prefrontal cortex (vmPFC) after craving induced by cue exposure during early abstinence (7-10 days) in ten women and forty-two men. The PAG is best known for its role in pain, avoidance, and defensive behaviors 186,187 .…”

Section: Discussionmentioning

confidence: 99%

Sex differences in opioid and psychostimulant craving and relapse: a critical review

Nicolas

Ne²,

Farokhnia

et al. 2021

Preprint

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A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies on sex differences in psychostimulant and opioid craving and relapse. Next, we review preclinical studies on sex differences in psychostimulant and opioid reinstatement of drug seeking after extinction of drug self-administration and incubation of drug craving (time-dependent increase in drug seeking during abstinence). We also discuss ovarian hormones’ role in relapse and craving in humans and animal models and speculate on brain mechanisms underlying their role in cocaine craving and relapse in rodent models. Finally, we discuss imaging studies on brain responses to cocaine cues and stress in men and women.The results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. However, this conclusion is tentative because most of the studies reviewed were correlational, not sufficiently powered, and/or not a priori designed to detect sex differences. Additionally, fMRI studies suggest sex differences in brain responses to cocaine cues and stress. The results of the preclinical studies reviewed provide evidence for sex differences in stress-induced reinstatement and incubation of cocaine craving, but not cue- or cocaine priming-induced reinstatement of cocaine seeking. These sex differences are modulated in part by ovarian hormones. In contrast, the available data do not support the notion of sex differences in craving and relapse/reinstatement for methamphetamine or heroin in rodent models.

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“…The Human Investigation Committee at Yale University School of Medicine approved the study procedures, and all participants signed an informed consent prior to study participation. Some of the subjects participated in our earlier studies ( Zhang et al, 2019 , 2020a , 2020b ).…”

Section: Methodsmentioning

confidence: 99%

Reward-Related Responses and Tonic Craving in Cocaine Addiction: An Imaging Study of the Monetary Incentive Delay Task

Zhornitsky

Dhingra

et al. 2021

International Journal of Neuropsychopharmacology

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Background Cocaine addiction is associated with altered sensitivity to natural reinforcers and intense drug craving. However, previous findings on reward-related responses are mixed and few studies have examined whether reward responses relate to tonic cocaine craving. Methods We combined fMRI and a monetary incentive delay task to investigate these issues. Imaging data were processed with published routines and the results were evaluated with a corrected threshold. We compared reward responses of 50 cocaine dependent individuals (CDs) and 45 healthy controls (HCs) for the ventral striatum (VS) and the whole brain. We also examined the regional responses in association with tonic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ) in CDs. We performed mediation analyses to evaluate the relationship between regional responses, CCQ score, and recent cocaine use. Results The VS showed higher activation to large as compared to small or no wins but this reward-related activity did not differ between CDs and HCs. The precentral gyrus (PCG), anterior insula, and supplementary motor area showed higher activation during large vs. no wins in positive correlation with the CCQ score in CDs. Mediation analyses suggested that days of cocaine use in the prior month contributed to higher CCQ scores and, in turn, PCG reward responses. Conclusions The results highlight a unique relationship between reward responses of the primary motor cortex, tonic cocaine craving and recent cocaine use. The motor cortex may partake in the cognitive motor processes critical to drug seeking behavior in addicted individuals.

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Cue-elicited functional connectivity of the periaqueductal gray and tonic cocaine craving

Cited by 13 publications

References 81 publications

Sex Differences in Substance Use Disorders: A Neurobiological Perspective

Sex Differences in Substance Use Disorders: A Neurobiological Perspective

Sex differences in opioid and psychostimulant craving and relapse: a critical review

Reward-Related Responses and Tonic Craving in Cocaine Addiction: An Imaging Study of the Monetary Incentive Delay Task

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