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Article ; Online: mGlu5 inhibition in the basolateral amygdala prevents estrous cycle-dependent changes in cue-induced cocaine seeking.

Corbett, Claire M / Miller, Emily N D / Loweth, Jessica A

Addiction neuroscience

2022 Volume 5

Abstract: Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced ... ...

Abstract	Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced craving and relapse vulnerability compared to males. In a rodent model of cocaine craving and relapse vulnerability, cue-induced cocaine seeking behavior following weeks of withdrawal from extended-access cocaine self-administration is higher in females in the estrus stage of the reproductive (estrous) cycle (Estrus Females) compared to both Males and females in all other stages (Non-Estrus Females). However, the neuronal substrates and cellular mechanisms underlying these sex differences is not fully understood. One region that contributes to both sex differences in behavioral responding and cue-induced cocaine seeking is the basolateral amygdala (BLA), while one receptor known to play a critical role in mediating cocaine seeking behavior is metabotropic glutamate receptor 5 (mGlu5). Here we assessed the effects of BLA mGlu5 inhibition following prolonged withdrawal from cocaine self-administration on observed estrous cycle-dependent changes in cue-induced cocaine seeking behavior. We found that BLA microinjections of the mGlu5 antagonist MTEP selectively reduced the enhanced cue-induced cocaine seeking normally observed in Estrus Females while having no effect on cocaine seeking in Males and Non-Estrus Females. These findings identify a unique interaction between cocaine-exposure, estrous cycle fluctuations and BLA mGlu5-dependent transmission on cue-induced cocaine seeking behavior.
Language	English
Publishing date	2022-12-06
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-3925
ISSN (online)	2772-3925
DOI	10.1016/j.addicn.2022.100055
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Editorial: Sex differences in the neurobiology of drug relapse vulnerability.

Manvich, Daniel F / Loweth, Jessica A / Lynch, Wendy J / McReynolds, Jayme R

Frontiers in behavioral neuroscience

2023 Volume 17, Page(s) 1289459

Language	English
Publishing date	2023-09-25
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2023.1289459
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Article ; Online: Effects of Sex and Estrous Cycle on the Time Course of Incubation of Cue-Induced Craving following Extended-Access Cocaine Self-Administration.

Corbett, Claire M / Dunn, Emily / Loweth, Jessica A

eNeuro

2021 Volume 8, Issue 4

Abstract: Cocaine addiction is a devastating public health epidemic that continues to grow. Studies focused on identifying biological factors influencing cocaine craving and relapse vulnerability are necessary to promote abstinence in recovering drug users. Sex ... ...

Abstract	Cocaine addiction is a devastating public health epidemic that continues to grow. Studies focused on identifying biological factors influencing cocaine craving and relapse vulnerability are necessary to promote abstinence in recovering drug users. Sex and ovarian hormones are known to influence cocaine addiction liability and relapse vulnerability in both humans and rodents. Previous studies have investigated sex differences in the time-dependent intensification or "incubation" of cue-induced cocaine craving that occurs during withdrawal from extended-access cocaine self-administration and have identified changes across the rat reproductive cycle (estrous cycle). Female rats in the estrus stage of the cycle (Estrus Females), the phase during which ovulation occurs, show an increase in the magnitude of incubated cue-induced cocaine craving compared with females in all other phases of the estrous cycle (Non-Estrus Females). Here we extend these findings by assessing incubated craving across the estrous cycle during earlier withdrawal periods (withdrawal day 1 and 15) and later withdrawal periods (withdrawal day 48). We found that this increase in the magnitude of incubated craving during estrus (Estrus Females) is present on withdrawal day 15, but not on withdrawal day 1, and further increases by withdrawal day 48. No difference in the magnitude of incubated craving was observed between Males and Non-Estrus Females. Our data indicate that the effects of hormonal fluctuations on cue-induced cocaine craving intensify during the first month and a half of withdrawal, showing an interaction among abstinence length, estrous cycle fluctuations, and cocaine craving.
MeSH term(s)	Animals ; Cocaine ; Cocaine-Related Disorders ; Craving ; Cues ; Estrous Cycle ; Female ; Male ; Rats
Chemical Substances	Cocaine (I5Y540LHVR)
Language	English
Publishing date	2021-08-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0054-21.2021
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Article ; Online: Perturbations in risk/reward decision making and frontal cortical catecholamine regulation induced by mild traumatic brain injury.

Knapp, Christopher P / Papadopoulos, Eleni / Loweth, Jessica A / Raghupathi, Ramesh / Floresco, Stan B / Waterhouse, Barry D / Navarra, Rachel L

Behavioural brain research

2024 Volume 467, Page(s) 115002

Abstract: Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is ... ...

Abstract	Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC. Rats were exposed to sham, single (smTBI), or three closed-head controlled cortical impact (CH-CCI) injuries and assessed for injury-induced effects on risk/reward decision making using a probabilistic discounting task (PDT). In the first week post-final surgery, mTBI increased risky choice preference. By the fourth week, males exhibited increased latencies to make risky choices following rmTBI, demonstrating a delayed effect on processing speed. When levels of tyrosine hydroxylase (TH) and the norepinephrine reuptake transporter (NET) were measured within subregions of the PFC, females exhibited dramatic increases of TH levels within the orbitofrontal cortex (OFC) following smTBI. However, both males and females demonstrated reduced levels of OFC NET following rmTBI. These results indicate the OFC is susceptible to catecholamine instability after rmTBI and suggests that not all areas of the PFC contribute equally to TBI-induced imbalances. Overall, the CH-CCI model of rmTBI has revealed time-dependent and sex-specific changes in risk/reward decision making and catecholamine regulation following repetitive mild head injuries.
Language	English
Publishing date	2024-04-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	449927-x
ISSN	1872-7549 ; 0166-4328
ISSN (online)	1872-7549
ISSN	0166-4328
DOI	10.1016/j.bbr.2024.115002
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Article: Age- and Sex-Dependent Changes in Locus Coeruleus Physiology and Anxiety-Like Behavior Following Acute Stressor Exposure.

Borodovitsyna, Olga / Tkaczynski, John A / Corbett, Claire M / Loweth, Jessica A / Chandler, Daniel J

Frontiers in behavioral neuroscience

2022 Volume 16, Page(s) 808590

Abstract: Adolescence is a critical period of development with increased sensitivity toward psychological stressors. Many psychiatric conditions emerge during adolescence and animal studies have shown that that acute stress has long-term effects on hypothalamic- ... ...

Abstract	Adolescence is a critical period of development with increased sensitivity toward psychological stressors. Many psychiatric conditions emerge during adolescence and animal studies have shown that that acute stress has long-term effects on hypothalamic-pituitary-adrenal axis function and behavior. We recently demonstrated that acute stress produces long-term electrophysiological changes in locus coeruleus and long-lasting anxiety-like behavior in adolescent male rats. Based on prior reports of increased stress sensitivity during adolescence and increased sensitivity of female locus coeruleus toward corticotropin releasing factor, we hypothesized that the same acute stressor would cause different behavioral and physiological responses in adolescent female and adult male and female rats one week after stressor exposure. In this study, we assessed age and sex differences in how an acute psychological stressor affects corticosterone release, anxiety-like behavior, and locus coeruleus physiology at short- and long-term intervals. All groups of animals except adult female responded to stress with elevated corticosterone levels at the acute time point. One week after stressor exposure, adolescent females showed decreased firing of locus coeruleus neurons upon current injection and increased exploratory behavior compared to controls. The results were in direct contrast to changes observed in adolescent males, which showed increased anxiety-like behavior and increased spontaneous and induced firing in locus coeruleus neurons a week after stressor exposure. Adult males and females were both behaviorally and electrophysiologically resilient to the long-term effects of acute stress. Therefore, there may be a normal developmental trajectory for locus coeruleus neurons which promotes stress resilience in adults, but stressor exposure during adolescence perturbs their function. Furthermore, while locus coeruleus neurons are more sensitive to stressor exposure during adolescence, the effect varies between adolescent males and females. These findings suggest that endocrine, behavioral, and physiological responses to stress vary among animals of different age and sex, and therefore these variables should be taken into account when selecting models and designing experiments to investigate the effects of stress. These differences in animals may also allude to age and sex differences in the prevalence of various psychiatric illnesses within the human population.
Language	English
Publishing date	2022-02-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2022.808590
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Article ; Online: Cocaine Exposure Increases Excitatory Synaptic Transmission and Intrinsic Excitability in the Basolateral Amygdala in Male and Female Rats and across the Estrous Cycle.

Corbett, Claire M / Miller, Emily N D / Wannen, Erin E / Rood, Benjamin D / Chandler, Daniel J / Loweth, Jessica A

Neuroendocrinology

2023 Volume 113, Issue 11, Page(s) 1127–1139

Abstract: Introduction: Sex and ovarian hormones influence cocaine seeking and relapse vulnerability, but less is known regarding the cellular and synaptic mechanisms contributing to these behavioral sex differences. One factor thought to influence cue-induced ... ...

Abstract	Introduction: Sex and ovarian hormones influence cocaine seeking and relapse vulnerability, but less is known regarding the cellular and synaptic mechanisms contributing to these behavioral sex differences. One factor thought to influence cue-induced seeking behavior following withdrawal is cocaine-induced changes in the spontaneous activity of pyramidal neurons in the basolateral amygdala (BLA). However, the mechanisms underlying these changes, including potential sex or estrous cycle effects, are unknown. Methods: Ex vivo whole-cell patch clamp electrophysiology was conducted to investigate the effects of cocaine exposure, sex, and estrous cycle fluctuations on two properties that can influence spontaneous activity of BLA pyramidal neurons: (1) frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) and (2) intrinsic excitability. Recordings of BLA pyramidal neurons were conducted in adult male and female rats and across the estrous cycle following 2-4 weeks of withdrawal from extended-access cocaine self-administration (6 h/day for 10 days) or drug-naïve conditions. Results: In both sexes, cocaine exposure increased the frequency, but not amplitude, of sEPSCs and neuronal intrinsic excitability. Across the estrous cycle, sEPSC frequency and intrinsic excitability were significantly elevated only in cocaine-exposed females in the estrus stage of the cycle, a stage when cocaine-seeking behavior is known to be enhanced. Conclusions: Here, we identify potential mechanisms underlying cocaine-induced alterations in the spontaneous activity of BLA pyramidal neurons in both sexes along with changes in these properties across the estrous cycle.
MeSH term(s)	Rats ; Animals ; Female ; Male ; Basolateral Nuclear Complex ; Cocaine/pharmacology ; Rats, Sprague-Dawley ; Synaptic Transmission ; Estrous Cycle
Chemical Substances	Cocaine (I5Y540LHVR)
Language	English
Publishing date	2023-06-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000531351
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Article ; Online: mGlu5 function in the nucleus accumbens core during the incubation of methamphetamine craving.

Murray, Conor H / Christian, Daniel T / Milovanovic, Mike / Loweth, Jessica A / Hwang, Eun-Kyung / Caccamise, Aaron J / Funke, Jonathan R / Wolf, Marina E

Neuropharmacology

2021 Volume 186, Page(s) 108452

Abstract: Many studies have demonstrated that negative allosteric modulators (NAM) of metabotropic glutamate receptor 5 (mGlu5) reduce cocaine and methamphetamine seeking in extinction-reinstatement animal models of addiction. Less is known about effects of mGlu5 ... ...

Abstract	Many studies have demonstrated that negative allosteric modulators (NAM) of metabotropic glutamate receptor 5 (mGlu5) reduce cocaine and methamphetamine seeking in extinction-reinstatement animal models of addiction. Less is known about effects of mGlu5 NAMs in abstinence models, particularly for methamphetamine. We used the incubation of drug craving model, in which cue-induced craving progressively intensifies after withdrawal from drug self-administration, to conduct the first studies of the following aspects of mGlu5 function in the rat nucleus accumbens (NAc) core during abstinence from methamphetamine self-administration: 1) functionality of the major form of synaptic depression in NAc medium spiny neurons, which is induced postsynaptically via mGlu5 and expressed presynaptically via cannabinoid type 1 receptors (CB1Rs), 2) mGlu5 surface expression and physical associations between mGlu5, Homer proteins, and diacylglycerol lipase-α, and 3) the effect of systemic and intra-NAc core administration of the mGlu5 NAM 3-((2-methyl-4-)ethynyl)pyridine (MTEP) on expression of incubated methamphetamine craving. We found that mGlu5/CB1R-dependent synaptic depression was lost during the rising phase of methamphetamine incubation but then recovered, in contrast to its persistent impairment during the plateau phase of incubation of cocaine craving. Furthermore, whereas the cocaine-induced impairment was accompanied by reduced mGlu5 levels and mGlu5-Homer associations, this was not the case for methamphetamine. Systemic MTEP reduced incubated methamphetamine seeking, but also reduced inactive hole nose-pokes and locomotion, while intra-NAc core MTEP had no significant effects. These findings provide the first insight into the role of mGlu5 in the incubation of methamphetamine craving and reveal differences from incubation of cocaine craving.
MeSH term(s)	Animals ; Craving/drug effects ; Craving/physiology ; Dopamine Uptake Inhibitors/administration & dosage ; Drug-Seeking Behavior/drug effects ; Drug-Seeking Behavior/physiology ; Male ; Methamphetamine/administration & dosage ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5/metabolism ; Self Administration
Chemical Substances	Dopamine Uptake Inhibitors ; Grm5 protein, rat ; Receptor, Metabotropic Glutamate 5 ; Methamphetamine (44RAL3456C)
Language	English
Publishing date	2021-01-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2021.108452
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Article ; Online: Cocaine and chronic stress exposure produce an additive increase in neuronal activity in the basolateral amygdala.

Munshi, Soumyabrata / Rosenkranz, J Amiel / Caccamise, Aaron / Wolf, Marina E / Corbett, Claire M / Loweth, Jessica A

Addiction biology

2019 Volume 26, Issue 1, Page(s) e12848

Abstract: Cocaine addiction is a chronic, relapsing disorder. Stress and cues related to cocaine are two common relapse triggers. We have recently shown that exposure to repeated restraint stress during early withdrawal accelerates the time-dependent ... ...

Abstract	Cocaine addiction is a chronic, relapsing disorder. Stress and cues related to cocaine are two common relapse triggers. We have recently shown that exposure to repeated restraint stress during early withdrawal accelerates the time-dependent intensification or "incubation" of cue-induced cocaine craving that occurs during the first month of withdrawal, although craving ultimately plateaus at the same level observed in controls. These data indicate that chronic stress exposure during early withdrawal may result in increased vulnerability to cue-induced relapse during this period. Previous studies have shown that chronic stress exposure in drug-naïve rats increases neuronal activity in the basolateral amygdala (BLA), a region critical for behavioral responses to stress. Given that glutamatergic projections from the BLA to the nucleus accumbens are critical for the incubation of cue-induced cocaine craving, we hypothesized that cocaine withdrawal and chronic stress exposure produce separate increases that additively increase BLA neuronal activity. To assess this, we conducted in vivo extracellular single-unit recordings from the BLA of anesthetized adult male rats following cocaine or saline self-administration (6 h/day for 10 days) and repeated restraint stress or control conditions on withdrawal days (WD) 6-14. Recordings were conducted from WD15 to WD20. Interestingly, cocaine exposure alone increased the spontaneous firing rate in the BLA to levels observed following chronic stress exposure in drug-naïve rats. Chronic stress exposure during cocaine withdrawal further increased firing rate. These studies may identify a potential mechanism by which both cocaine and chronic stress exposure drive cue-induced relapse vulnerability during abstinence.
MeSH term(s)	Animals ; Basolateral Nuclear Complex/physiopathology ; Cocaine ; Cocaine-Related Disorders/physiopathology ; Craving/physiology ; Cues ; Drug-Seeking Behavior/physiology ; Male ; Neurons/physiology ; Nucleus Accumbens/physiology ; Rats ; Self Administration ; Stress, Psychological/physiopathology ; Substance Withdrawal Syndrome
Chemical Substances	Cocaine (I5Y540LHVR)
Language	English
Publishing date	2019-11-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1324314-7
ISSN	1369-1600 ; 1355-6215
ISSN (online)	1369-1600
ISSN	1355-6215
DOI	10.1111/adb.12848
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Zs.A 4586: Show issues

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Article ; Online: BDNF contributes to both rapid and homeostatic alterations in AMPA receptor surface expression in nucleus accumbens medium spiny neurons.

Reimers, Jeremy M / Loweth, Jessica A / Wolf, Marina E

The European journal of neuroscience

2014 Volume 39, Issue 7, Page(s) 1159–1169

Abstract: Brain-derived neurotrophic factor (BDNF) plays a critical role in plasticity at glutamate synapses and in the effects of repeated cocaine exposure. We recently showed that intracranial injection of BDNF into the rat nucleus accumbens (NAc), a key region ... ...

Abstract	Brain-derived neurotrophic factor (BDNF) plays a critical role in plasticity at glutamate synapses and in the effects of repeated cocaine exposure. We recently showed that intracranial injection of BDNF into the rat nucleus accumbens (NAc), a key region for cocaine addiction, rapidly increases α-amino-3-hyroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) surface expression. To further characterize BDNF's role in both rapid AMPAR trafficking and slower, homeostatic changes in AMPAR surface expression, we investigated the effects of acute (30 min) and long-term (24 h) treatment with BDNF on AMPAR distribution in NAc medium spiny neurons from postnatal rats co-cultured with mouse prefrontal cortex neurons to restore excitatory inputs. Immunocytochemical studies showed that acute BDNF treatment increased cell surface GluA1 and GluA2 levels, as well as their co-localization, on NAc neurons. This effect of BDNF, confirmed using a protein crosslinking assay, was dependent on ERK but not AKT signaling. In contrast, long-term BDNF treatment decreased AMPAR surface expression on NAc neurons. Based on this latter result, we tested the hypothesis that BDNF plays a role in AMPAR 'scaling down' in response to a prolonged increase in neuronal activity produced by bicuculline (24 h). Supporting this hypothesis, decreasing BDNF signaling with the extracellular BDNF scavenger TrkB-Fc prevented the scaling down of GluA1 and GluA2 surface levels in NAc neurons normally produced by bicuculline. In conclusion, BDNF exerts bidirectional effects on NAc AMPAR surface expression, depending on duration of exposure. Furthermore, BDNF's involvement in synaptic scaling in the NAc differs from its previously described role in the visual cortex.
MeSH term(s)	Animals ; Bicuculline/pharmacology ; Brain-Derived Neurotrophic Factor/pharmacology ; Cells, Cultured ; Excitatory Postsynaptic Potentials ; Homeostasis ; Mice ; Neurons/drug effects ; Neurons/metabolism ; Neurons/physiology ; Nucleus Accumbens/cytology ; Nucleus Accumbens/metabolism ; Protein Transport ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/metabolism ; Synaptic Membranes/metabolism
Chemical Substances	Brain-Derived Neurotrophic Factor ; Receptors, AMPA ; Bicuculline (Y37615DVKC)
Language	English
Publishing date	2014-04-08
Publishing country	France
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.12422
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Article ; Online: Adaptations in AMPA receptor transmission in the nucleus accumbens contributing to incubation of cocaine craving.

Loweth, Jessica A / Tseng, Kuei Y / Wolf, Marina E

Neuropharmacology

2013 Volume 76 Pt B, Page(s) 287–300

Abstract: Cue-induced cocaine craving in rodents intensifies or "incubates" during the first months of withdrawal from long access cocaine self-administration. This incubation phenomenon is relevant to human users who achieve abstinence but exhibit persistent ... ...

Abstract	Cue-induced cocaine craving in rodents intensifies or "incubates" during the first months of withdrawal from long access cocaine self-administration. This incubation phenomenon is relevant to human users who achieve abstinence but exhibit persistent vulnerability to cue-induced relapse. It is well established that incubation of cocaine craving involves complex neuronal circuits. Here we will focus on neuroadaptations in the nucleus accumbens (NAc), a region of convergence for pathways that control cocaine seeking. A key adaptation is a delayed (~3-4 weeks) accumulation of Ca(2+)-permeable AMPAR receptors (CP-AMPARs) in synapses on medium spiny neurons (MSN) of the NAc. These CP-AMPARs mediate the expression of incubation after prolonged withdrawal, although different mechanisms must be responsible during the first weeks of withdrawal, prior to CP-AMPAR accumulation. The cascade of events leading to CP-AMPAR accumulation is still unclear. However, several candidate mechanisms have been identified. First, mGluR1 has been shown to negatively regulate CP-AMPAR levels in NAc synapses, and it is possible that a withdrawal-dependent decrease in this effect may help explain CP-AMPAR accumulation during incubation. Second, an increase in phosphorylation of GluA1 subunits (at the protein kinase A site) within extrasynaptic homomeric GluA1 receptors (CP-AMPARs) may promote their synaptic insertion and oppose their removal. Finally, elevation of brain-derived neurotrophic factor (BDNF) levels in the NAc may contribute to maintenance of incubation after months of withdrawal, although incubation-related increases in BDNF accumulation do not account for CP-AMPAR accumulation. Receptors and pathways that negatively regulate incubation, such as mGluR1, are promising targets for the development of therapeutic strategies to help recovering addicts maintain abstinence. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.
MeSH term(s)	Adaptation, Physiological/physiology ; Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Cocaine-Related Disorders/physiopathology ; Drug-Seeking Behavior/physiology ; Humans ; Nucleus Accumbens/metabolism ; Receptors, AMPA/metabolism
Chemical Substances	Brain-Derived Neurotrophic Factor ; Receptors, AMPA
Language	English
Publishing date	2013-05-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2013.04.061
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