Hippocampal mu opioid receptors are modulated following cocaine self‐administration in rat

Nogueira, David De Sa; Bourdy, Romain; Filliol, Dominique; Romieu, Pascal; Befort, Katia

doi:10.1111/ejn.15217

Cited by 4 publications

(4 citation statements)

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“…The blockade of κ opioid receptors selectively attenuated increased cocaine self-administration in rats with extended access to cocaine [ 66 ]. In addition, it has recently been demonstrated that, following self-administration in rats, cocaine modulates hippocampal mu opioid receptors [ 67 ].…”

Section: Resultsmentioning

confidence: 99%

Understanding the Mechanisms of Action and Effects of Drugs of Abuse

et al. 2023

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Aim. Drug abuse and addiction are major public health concerns, with millions of people worldwide affected by the negative consequences of drug use. To better understand this complex issue, a review was conducted to examine the mechanisms of action and effects of drugs of abuse, including their acute and chronic effects, the symptoms of abstinence syndrome, as well as their cardiovascular impacts. Methods. The analyzed data were obtained after surveying an electronic database, namely PubMed, with no time limit, grey literature sources, and reference lists of relevant articles. Results. The review highlights the different categories of drugs of abuse, such as opioids, stimulants, depressants, hallucinogens, and cannabis, and discusses the specific ways that each drug affects the brain and body. Additionally, the review explores the short-term and long-term effects of drug abuse on the body and mind, including changes in brain structure and function, physical health problems, and mental health issues, such as depression and anxiety. In addition, the review explores the effects of drug abuse on cardiovascular health, focusing on electrocardiogram changes. Moreover, the analysis of relevant literature also highlighted possible genetic susceptibility in various addictions. Furthermore, the review delves into the withdrawal symptoms that occur when someone stops using drugs of abuse after a period of chronic use. Conclusion. Overall, this review provides a comprehensive overview of the current state of knowledge on drug abuse and addiction. The findings of this review can inform the development of evidence-based prevention and intervention strategies to address this critical public health issue.

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Section: Resultsmentioning

confidence: 99%

Understanding the Mechanisms of Action and Effects of Drugs of Abuse

et al. 2023

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“…Moreover, they found that conditional overexpression of MORs in DG neural stem cells led to enhanced morphine self‐administration, confirming the role of DG MORs in the establishment of morphine addiction. 269 Furthermore, another two studies reported that cocaine addiction increased the MORs expression and functionality in the rat hippocampus, 270 and adolescent morphine exposure enhanced the MORs‐mediated G‐protein activity in the hippocampus and morphine preference in the conditioned place preference test in adult mice. 271 These two studies provide us with a glimpse of hippocampal MORs alteration under drug addiction situations.…”

Section: Reward Circuitry Addiction and Morsmentioning

confidence: 99%

Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu‐opioid receptor

Zhang

Song

Dai

et al. 2022

MedComm

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Opioid abuse and addiction have become a global pandemic, posing tremendous health and social burdens. The rewarding effects and the occurrence of withdrawal symptoms are the two mainstays of opioid addiction. Mu‐opioid receptors (MORs), a member of opioid receptors, play important roles in opioid addiction, mediating both the rewarding effects of opioids and opioid withdrawal syndrome (OWS). The underlying mechanism of MOR‐mediated opioid rewarding effects and withdrawal syndrome is of vital importance to understand the nature of opioid addiction and also provides theoretical basis for targeting MORs to treat drug addiction. In this review, we first briefly introduce the basic concepts of MORs, including their structure, distribution in the nervous system, endogenous ligands, and functional characteristics. We focused on the brain circuitry and molecular mechanism of MORs‐mediated opioid reward and withdrawal. The neuroanatomical and functional elements of the neural circuitry of the reward system underlying opioid addiction were thoroughly discussed, and the roles of MOR within the reward circuitry were also elaborated. Furthermore, we interrogated the roles of MORs in OWS, along with the structural basis and molecular adaptions of MORs‐mediated withdrawal syndrome. Finally, current treatment strategies for opioid addiction targeting MORs were also presented.

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“…Samples (n=5-7/group) were prepared as previously described [51] with minor modifications. Briefly, frozen tissues were ground on carbonic ice before fixation (1% formaldehyde) and quenched with glycine (0.125M).…”

Section: Epigenetic Analysis 251 Chromatin Immunoprecipitationmentioning

confidence: 99%

“…Samples were washed and reverse cross-linking was performed at 65°C overnight, and DNA purified (DNA mini elute kit, Qiagen, France). Additionally, a negative control without IgG was performed to test for nonspecific binding [51]. The % of enrichment was calculated as follow: (signal H3K27acsignal no ab)/Input *100.…”

Section: Epigenetic Analysis 251 Chromatin Immunoprecipitationmentioning

confidence: 99%

Hippocampal Cannabinoid 1 Receptors Are Modulated Following Cocaine Self-administration in Male Rats

et al. 2022

Self Cite

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Cocaine addiction is a complex pathology inducing long-term neuroplastic changes that, in. turn, contribute to maladaptive behaviors. This behavioral dysregulation is associated with transcriptional reprogramming in brain reward circuitry, although the mechanisms underlying this modulation remain poorly understood. The endogenous cannabinoid system may play a role in this process in that cannabinoid mechanisms modulate drug reward and contribute to cocaine-induced neural adaptations. In this study, we investigated whether cocaine selfadministration induces long-term adaptations, including transcriptional modifications and associated epigenetic processes. We first examined endocannabinoid gene expression in reward-related brain regions of the rat following self-administered (0.33mg/kg intravenous, FR1, 10 days) cocaine injections. Interestingly, we found increased Cnr1 expression in several structures, including prefrontal cortex, nucleus accumbens, dorsal striatum, hippocampus, habenula, amygdala, lateral hypothalamus, ventral tegmental area and rostromedial tegmental nucleus, with most pronounced effects in the hippocampus.Endocannabinoid levels, measured by mass spectrometry, were also altered in this structure.Chromatin immunoprecipitation followed by qPCR in the hippocampus revealed that two activating histone marks, H3K4Me3 and H3K27Ac, were enriched at specific endocannabinoid genes following cocaine intake. Targeting CB1 receptors using chromosome conformation capture, we highlighted spatial chromatin re-organization in the hippocampus, as well as in the nucleus accumbens, suggesting that destabilization of the chromatin may contribute to neuronal responses to cocaine. Overall, our results highlight a key role for the hippocampus in cocaine-induced plasticity and broaden the understanding of neuronal alterations associated with endocannabinoid signaling. The latter suggests that epigenetic modifications contribute to maladaptive behaviors associated with chronic drug use.

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Hippocampal mu opioid receptors are modulated following cocaine self‐administration in rat

Cited by 4 publications

References 65 publications

Understanding the Mechanisms of Action and Effects of Drugs of Abuse

Understanding the Mechanisms of Action and Effects of Drugs of Abuse

Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu‐opioid receptor

Hippocampal Cannabinoid 1 Receptors Are Modulated Following Cocaine Self-administration in Male Rats

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