The Winding Road to Relapse: Forging a New Understanding of Cue-Induced Reinstatement Models and Their Associated Neural Mechanisms

Namba, Mark D.; Tomek, Seven E.; Olive, M. Foster; Beckmann, Joshua S.; Gipson, Cassandra D.

doi:10.3389/fnbeh.2018.00017

Cited by 41 publications

(39 citation statements)

References 278 publications

(274 reference statements)

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“…In contrast, another recent study demonstrated that nicotine consumption in rats is negatively correlated with α7 expression within the HPC, which is most prominent in females (Gozen et al, 2016). Indeed, the heterogeneity of nAChR expression throughout the brain as well as the differential neurobehavioral impact of experimenter-delivered drug exposure versus self-administration likely contributed to these seemingly discrepant findings (Gotti et al, 2009;Namba et al, 2018). Additionally, such differences may suggest that nicotine alters α7-containing nAChR expression differentially throughout the brain, which could produce brain region-specific differences in downstream neuroimmune signaling.…”

Section: Nicotinementioning

confidence: 97%

Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities

et al. 2021

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Recent studies examining the neurobiology of substance abuse have revealed a significant role of neuroimmune signaling as a mechanism through which drugs of abuse induce aberrant changes in synaptic plasticity and contribute to substance abuse-related behaviors. Immune signaling within the brain and the periphery critically regulates homeostasis of the nervous system. Perturbations in immune signaling can induce neuroinflammation or immunosuppression, which dysregulate nervous system function including neural processes associated with substance use disorders (SUDs). In this review, we discuss the literature that demonstrates a role of neuroimmune signaling in regulating learning, memory, and synaptic plasticity, emphasizing specific cytokine signaling within the central nervous system. We then highlight recent preclinical studies, within the last 5 years when possible, that have identified immune mechanisms within the brain and the periphery associated with addiction-related behaviors. Findings thus far underscore the need for future investigations into the clinical potential of immunopharmacology as a novel approach toward treating SUDs. Considering the high prevalence rate of comorbidities among those with SUDs, we also discuss neuroimmune mechanisms of common comorbidities associated with SUDs and highlight potentially novel treatment targets for these comorbid conditions. We argue that immunopharmacology represents a novel frontier in the development of new pharmacotherapies that promote long-term abstinence from drug use and minimize the detrimental impact of SUD comorbidities on patient health and treatment outcomes.

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Section: Nicotinementioning

confidence: 97%

Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities

et al. 2021

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“…the reinstatement of both paradigms suggests a dissociation of the neurobiological mechanisms mediating these behaviours. Indeed, many reviews have discussed the different brain circuitry recruited during drug-primed, cue-primed or combined drug-and cue-primed reinstatement of drug seeking (Brown and Lawrence, 2009;Namba et al, 2018;Stewart, 2008). No previous studies have investigated the role of α7 nAChRs in opiate drug-seeking, whereas there is a limited literature for other psychoactive substances.…”

Section: Drug Craving Pharmacological Tolerancementioning

confidence: 99%

“…However, reinstatement of drug-seeking involves the re-establishment of goal-directed behaviours, mediated, in large part, by interconnections between a number of brain regions that are common to reinstatement across all drugs of abuse (prefrontal cortex, hippocampus, nucleus accumbens, amygdala, ventral tegmental area (Koob and Volkow, 2016;Namba et al, 2018)). There are differences in how initiators of the reinstatement of drug-seeking, e.g.…”

Section: Introductionmentioning

confidence: 99%

Contrasting effects of the α7 nicotinic receptor antagonist methyllycaconitine in different rat models of heroin reinstatement

et al. 2021

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Background: α7 Nicotinic acetylcholine receptors are implicated in the reinstatement of drug-seeking, an important component of relapse. We showed previously that the α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, specifically attenuated morphine-primed reinstatement of conditioned place preference in rodents and this effect was mediated in the ventral hippocampus. Aims: The purpose of this study was to evaluate α7 nicotinic acetylcholine receptor antagonism in reinstatement of the conditioned place preference for the more widely abused opioid, heroin, and to compare the effect of α7 nicotinic acetylcholine receptor blockade on reinstatement of heroin-seeking and heroin self-administration in an intravenous self-administration model of addictive behaviour. Methods: Rats were trained to acquire heroin conditioned place preference or heroin self-administration; both followed by extinction of responding. Methyllycaconitine or saline was given prior to reinstatement of drug-primed conditioned place preference, or drug-prime plus cue-induced reinstatement of intravenous self-administration, using two protocols: without delivery of heroin in response to lever pressing to model heroin-seeking, or with heroin self-administration, using fixed and progressive ratio reward schedules, to model relapse. Results: Methyllycaconitine had no effect on acquisition of heroin conditioned place preference or lever-pressing for food rewards. Methyllycaconitine blocked reinstatement of heroin-primed conditioned place preference. Methyllycaconitine did not prevent drug-prime plus cue-induced reinstatement of heroin-seeking, reinstatement of heroin self-administration, or diminish the reinforcing effect of heroin. Conclusions: The α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, prevented reinstatement of the opioid conditioned place preference, consistent with a role for α7 nicotinic acetylcholine receptors in the retrieval of associative memories of drug liking. The lack of effect of methyllycaconitine in heroin-dependent rats in two intravenous self-administration models suggests that α7 nicotinic acetylcholine receptors do not play a role in later stages of heroin abuse.

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“…In alcohol addiction, cues that are associated with alcohol trigger craving and the relapse (George & Koob, 2010;Namba et al, 2018). Alcohol induces multiple alterations in the brain that are thought to contribute to addiction, but an understanding of the neuronal ensembles responsible for excessive alcohol drinking is still preliminary (George & Hope, 2017).…”

Section: Introductionmentioning

confidence: 99%

A whole-brain imaging-based systems approach to understand origin of addiction in binge-like drinking model

Stefaniuk¹,

Pawłowska

Nowicka³

et al. 2021

Preprint

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Many fundamental questions on addiction development are still unanswered. These questions are frequently difficult to address by examining a single brain structure, but can best be addressed at the systems level. Neurons create functional networks that change over time, since brain regions may work together differently in different contexts. We offer a framework for describing the nature behind alcohol binge drinking and the transition to addiction. The present study investigated whole-brain c-Fos expression following reexposure to alcohol in a model of binge-like drinking in mice in IntelliCage. We developed a dedicated image computational workflow to identify c-Fos-positive cells in three-dimensional images obtained after optical tissue clearing and whole-brain imaging in the light-sheet microscope. We analyzed functional networks and brain modularity following reexposure to alcohol. c-Fos levels in brains from animals that were reexposed to alcohol were clearly different from binge drinking animals. Structures involved in reward processing, decision making and characteristic for addictive behaviors stood out particularly. In alcohol reexposed animals differently active structures either gained or lost correlation when compared to the control group.

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The Winding Road to Relapse: Forging a New Understanding of Cue-Induced Reinstatement Models and Their Associated Neural Mechanisms

Cited by 41 publications

References 278 publications

Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities

Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities

Contrasting effects of the α7 nicotinic receptor antagonist methyllycaconitine in different rat models of heroin reinstatement

A whole-brain imaging-based systems approach to understand origin of addiction in binge-like drinking model

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