| 1. |
- Adermark, Louise, 1974, et al.
(författare)
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Acute and chronic modulation of striatal endocannabinoid-mediated plasticity by nicotine.
- 2019
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Ingår i: Addiction biology. - : Wiley. - 1369-1600 .- 1355-6215. ; 24:3, s. 355-363
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Tidskriftsartikel (refereegranskat)abstract
- The endocannabinoid (eCB) system modulates several phenomena related to addictive behaviors, and drug-induced changes in eCB signaling have been postulated to be important mediators of physiological and pathological reward-related synaptic plasticity. Here, we studied eCB-mediated long-term depression (eCB-LTD) in the dorsolateral striatum, a brain region critical for acquisition of habitual and automatic behavior. We report that nicotine differentially affects ex vivo eCB signaling depending on previous exposure in vivo. In the nicotine-naïve brain, nicotine facilitates eCB-signaling and LTD, whereas tolerance develops to this facilitating effect after subchronic exposure in vivo. In the end, a progressive impairment of eCB-induced LTD is established after protracted withdrawal from nicotine. Endocannabinoid-LTD is reinstated 6months after the last drug injection, but a brief period of nicotine re-exposure is sufficient to yet again impair eCB-signaling. LTD induced by the cannabinoid 1 receptor agonist WIN55,212-2 is not affected, suggesting that nicotine modulates eCB production or release. Nicotine-induced facilitation of eCB-LTD is occluded by the dopamine D2 receptor agonist quinpirole, and by the muscarinic acetylcholine receptor antagonist scopolamine. In addition, the same compounds restore eCB-LTD during protracted withdrawal. Nicotine may thus modulate eCB-signaling by affecting dopaminergic and cholinergic neurotransmission in a long-lasting manner. Overall, the data presented here suggest that nicotine facilitates eCB-LTD in the initial phase, which putatively could promote neurophysiological and behavioral adaptations to the drug. Protracted withdrawal, however, impairs eCB-LTD, which may influence or affect the ability to maintain cessation.
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| 2. |
- Adermark, Louise, 1974, et al.
(författare)
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Temporal Rewiring of Striatal Circuits Initiated by Nicotine
- 2016
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Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X .- 1740-634X. ; 41:13, s. 3051-3059
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Tidskriftsartikel (refereegranskat)abstract
- Drug addiction has been conceptualized as maladaptive recruitment of integrative circuits coursing through the striatum, facilitating drug-seeking and drug-taking behavior. The aim of this study was to define temporal neuroadaptations in striatal subregions initiated by 3 weeks of intermittent nicotine exposure followed by protracted abstinence. Enhanced rearing activity was assessed in motor activity boxes as a measurement of behavioral change induced by nicotine (0.36 mg/kg), whereas electrophysiological field potential recordings were performed to evaluate treatment effects on neuronal activity. Dopamine receptor mRNA expression was quantified by qPCR, and nicotine-induced dopamine release was measured in striatal subregions using in vivo microdialysis. Golgi staining was performed to assess nicotine-induced changes in spine density of medium spiny neurons. The data presented here show that a brief period of nicotine exposure followed by abstinence leads to temporal changes in synaptic efficacy, dopamine receptor expression, and spine density in a subregion-specific manner. Nicotine may thus initiate a reorganization of striatal circuits that continues to develop despite protracted abstinence. We also show that the response to nicotine is modulated in previously exposed rats even after 6 months of abstinence. The data presented here suggests that, even though not self-administered, nicotine may produce progressive neuronal alterations in brain regions associated with goal-directed and habitual performance, which might contribute to the development of compulsive drug seeking and the increased vulnerability to relapse, which are hallmarks of drug addiction.
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| 3. |
- Alimoradi, Zainab, et al.
(författare)
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Estimation of Behavioral Addiction Prevalence During COVID-19 Pandemic : A Systematic Review and Meta-analysis
- 2022
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Ingår i: Current Addiction Reports. - : Springer. - 2196-2952. ; 9, s. 486-517
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of ReviewThe COVID-19 pandemic changed people's lifestyles and such changed lifestyles included the potential of increasing addictive behaviors. The present systematic review and meta-analysis aimed to estimate the prevalence of different behavioral addictions (i.e., internet addiction, smartphone addiction, gaming addiction, social media addiction, food addiction, exercise addiction, gambling addiction, and shopping addiction) both overall and separately.Recent FindingsFour databases (PubMed, Scopus, ISI Web of Knowledge, and ProQuest) were searched. Peer-reviewed papers published in English between December 2019 and July 2022 were reviewed and analyzed. Search terms were selected using PECO-S criteria: population (no limitation in participants' characteristics), exposure (COVID-19 pandemic), comparison (healthy populations), outcome (frequency or prevalence of behavioral addiction), and study design (observational study). A total of 94 studies with 237,657 participants from 40 different countries (mean age 25.02 years; 57.41% females). The overall prevalence of behavioral addiction irrespective of addiction type (after correcting for publication bias) was 11.1% (95% CI: 5.4 to 16.8%). The prevalence rates for each separate behavioral addiction (after correcting for publication bias) were 10.6% for internet addiction, 30.7% for smartphone addiction, 5.3% for gaming addiction, 15.1% for social media addiction, 21% for food addiction, 9.4% for sex addiction, 7% for exercise addiction, 7.2% for gambling addiction, and 7.2% for shopping addiction. In the lockdown periods, prevalence of food addiction, gaming addiction, and social media addiction was higher compared to non-lockdown periods. Smartphone and social media addiction was associated with methodological quality of studies (i.e., the higher the risk of boas, the higher the prevalence rate). Other associated factors of social media addiction were the percentage of female participants, mean age of participants, percentage of individuals using the internet in country, and developing status of country. The percentage of individuals in the population using the internet was associated with all the prevalence of behavioral addiction overall and the prevalence of sex addiction and gambling addiction. Gaming addiction prevalence was associated with data collection method (online vs. other methods) that is gaming addiction prevalence was much lower using online methods to collect the data.SummaryBehavioral addictions appeared to be potential health issues during the COVID-19 pandemic. Healthcare providers and government authorities should foster some campaigns that assist people in coping with stress during COVID-19 pandemics to prevent them from developing behavioral addictions during COVID-19 and subsequent pandemics.
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| 4. |
- Clarke, Rhona B. C., et al.
(författare)
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Involvement of Inhibitory Receptors in Modulating Dopamine Signaling and Synaptic Activity Following Acute Ethanol Exposure in Striatal Subregions
- 2015
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Ingår i: Alcoholism-Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 39:12, s. 2364-2374
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alcohol acts on both inhibitory and excitatory receptor systems resulting in a net increase in dopamine output in the ventral striatum (nucleus accumbens [nAc]), which is implicated in drug reward. However, the dorsal striatum may also be involved in reward-related behaviors. The objectives of this study were to investigate the role of inhibitory receptors in modulating the acute effects of ethanol (EtOH) on dopamine release and synaptic activity in the shell region of the nAc (nAcS) and dorsolateral striatum (DLS). Methods: EtOH (300 mM) was administered via reversed microdialysis in the nAcS or DLS of Wistar rats following pretreatment with glycine or GABA(A) receptor antagonist strychnine and bicuculline, respectively. Dopamine content in dialysate samples was quantified using high-performance liquid chromatography. In addition, local field potential recordings were performed in the nAcS and DLS in slices from Wistar rats. Population spike (PS) amplitude was measured following treatment with EtOH (50 mM) in slices pretreated with strychnine or bicuculline. Results: Local EtOH increased dopamine levels in both regions, an effect that strychnine pretreatment inhibited in the nAcS. EtOH-induced increases in accumbal dopamine were not blocked by a low (5 mu M) concentration of bicuculline, but were inhibited by pretreatment with higher bicuculline concentrations. None of the antagonists administered in the DLS prevented the EtOH-induced dopamine increase. Field potential recordings in the nAcS showed that acute EtOH produced an increase in PS amplitude which was blocked by both strychnine and bicuculline. In the DLS, EtOH induced a decrease in PS amplitude which was not influenced by strychnine or bicuculline. Conclusions: The current results show that changes in striatal dopamine output and synaptic activity induced by acute EtOH administration are modulated by inhibitory receptors in a subregion-specific manner.
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| 5. |
- Licheri, Valentina, et al.
(författare)
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Complex Control of Striatal Neurotransmission by Nicotinic Acetylcholine Receptors via Excitatory Inputs onto Medium Spiny Neurons
- 2018
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 38:29, s. 6597-6607
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of nicotine dependence is higher than that for any other substance abuse disorder; still, the underlying mechanisms are not fully established. To this end, we studied acute effects by nicotine on neurotransmission in the dorsolateral striatum, a key brain region with respect to the formation of habits. Electrophysiological recordings in acutely isolated brain slices from rodent showed that nicotine (10 nM to 10 mu M) produced an LTD of evoked field potentials. Current-clamp recordings revealed no significant effect by nicotine on membrane voltage or action potential frequency, indicating that the effect by nicotine is primarily synaptic. Nicotine did not modulate sIPSCs, or the connectivity between fast-spiking interneurons and medium spiny neurons, as assessed by whole-cell recordings combined with optogenetics. However, the frequency of sEPSCs was significantly depressed by nicotine. The effect by nicotine was mimicked by agonists targeting alpha 7-or alpha 4-containing nAChRs and blocked in slices pretreated with a mixture of antagonists targeting these receptor subtypes. Nicotine-induced LTD was furthermore inhibited by dopamine D2 receptor antagonist and occluded by D2 receptor agonist. In addition, modulation of cholinergic neurotransmission suppressed the responding to nicotine, which might reflect upon the postulated role for nAChRs as a presynaptic filter to differentially govern dopamine release depending on neuronal activity. Nicotine-induced suppression of excitatory inputs onto medium spiny neurons may promote nicotine-induced locomotor stimulation and putatively initiate neuroadaptations that could contribute to the transition toward compulsive drug taking.
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| 6. |
- Lotfi, Amir, et al.
(författare)
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Sustained inhibitory transmission but dysfunctional dopamine D2 receptor signaling in dorsal striatal subregions following protracted abstinence from amphetamine
- 2022
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Ingår i: Pharmacology Biochemistry and Behavior. - : Elsevier BV. - 0091-3057. ; 218
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Tidskriftsartikel (refereegranskat)abstract
- Behavioral sensitization to amphetamine is a complex phenomenon that engages several neurotransmitter systems and brain regions. While dysregulated signaling in the mesolimbic dopamine system repeatedly has been linked to behavioral sensitization, later research has implicated dorsal striatal circuits and GABAergic neurotransmission in contributing to behavioral transformation elicited by amphetamine. The aim of this study was thus to determine if repeated amphetamine exposure followed by abstinence would alter inhibitory neurotransmission in dorsal striatal subregions. To this end, male Wistar rats received amphetamine (2.0 mg/kg) in an intermittent manner for a total of five days. Behavioral sensitization to amphetamine was measured in locomotor-activity boxes, while neuroadaptations were recorded in the dorsolateral (DLS) and dorsomedial striatum (DMS) using ex vivo electrophysiology at different timepoints of amphetamine abstinence (2 weeks, 4-5 weeks, 10-11 weeks). Data show that repeated drug-exposure produces behavioral sensitization to the locomotor-stimulatory properties of amphetamine, which sustains for at least ten weeks. Electrophysiological recordings demonstrated a long-lasting suppression of evoked population spikes in both striatal subregions. Furthermore, following ten weeks of abstinence, the responsiveness to a dopamine D2 receptor agonist was significantly impaired in brain slices from rats previously receiving amphetamine. However, neither the frequency nor the amplitude of spontaneous inhibitory currents was affected by treatment at any of the time points analyzed. In conclusion, passive administration of amphetamine initiates long-lasting neuroadaptations in brain regions associated with goal-directed behavior and habitual performance, but these transformations do not appear to be driven by changes in GABAergic neurotransmission.
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| 7. |
- Lotfi Moghaddam, Amir
(författare)
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Acute and chronic effects by stimulants on behavior and striatal neurotransmission in the rat
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nicotine and amphetamines are the most widely abused stimulants. The main aim of the studies in this thesis was to investigate how these two drugs of abuse affect distinct regions of the rat brain involved in development of habitual and compulsive behavior, namely subregions of striatum in the rat. To this end, using a battery of tests including behavior, brain slice electrophysiology, and molecular biology, we have evaluated acute effects by nicotine and amphetamine, as well as progressive changes induced by their chronic use and discontinuation. We show that nicotine acutely depresses synaptic activity in dorsal striatum, an effect that involves multiple receptors. In chronic experiments, we show that a brief exposure to nicotine (15 days) or amphetamine (five days) induces persistent behavioral changes, which sustain over long periods of withdrawal. In addition, we demonstrate that following the drug exposure period, dorsal striatal subregions are engaged in a temporal manner, such that effects in lateral portions only appear after protracted withdrawal, where they sustain for a long time. We also demonstrate that drug-induced effects on behavior and synaptic activity are enhanced in younger animals. In summary, we show acute and long-lasting effects by stimulants on behavior and neurotransmission in striatal subregions, where they also reveal spatiotemporal and age-dependent components.
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