scholarly journals Alterations of Amphetamine Reward by Prior Nicotine and Alcohol Treatment: The Role of Age and Dopamine

2021 ◽  
Vol 11 (4) ◽  
pp. 420
Author(s):  
Andrea Stojakovic ◽  
Syed Muzzammil Ahmad ◽  
Kabirullah Lutfy

Evidence suggests that nicotine and alcohol can each serve as a gateway drug. We determined whether prior nicotine and alcohol treatment would alter amphetamine reward. Also, we examined whether age and dopaminergic neurotransmission are important in this regard. Male and female adolescent and adult C57BL/6J mice were tested for baseline place preference. Mice then received six conditioning with saline/nicotine (0.25 mg/kg) twice daily, followed by six conditioning with saline/ethanol (2 g/kg). Control mice were conditioned with saline/saline throughout. Finally, mice were conditioned with amphetamine (3 mg/kg), once in the nicotine-alcohol-paired chamber, and tested for place preference 24 h later. The following day, mice were challenged with amphetamine (1 mg/kg) and tested for place preference under a drugged state. Mice were then immediately euthanized, their brain removed, and nucleus accumbens isolated and processed for the level of dopamine receptors and transporter and glutamate receptors. We observed a greater amphetamine-induced place preference in naïve adolescents than adult mice with no change in state-dependent place preference between the two age groups. In contrast, amphetamine induced a significant place preference in adult but not adolescent mice with prior nicotine-alcohol exposure under the drug-free state. The preference was significantly greater in adults than adolescents under the drugged state. The enhanced response was associated with higher dopamine-transporter and D1 but reduced D2 receptors’ expression in adult rather than adolescent mice, with no changes in glutamate receptors levels. These results suggest that prior nicotine and alcohol treatment differentially alters amphetamine reward in adult and adolescent mice. Alterations in dopaminergic neurotransmission may be involved in this phenotype.

2020 ◽  
Author(s):  
Andrea Stojakovic ◽  
Syed Muzzammil Ahmad ◽  
Kabirullah Lutfy

AbstractRationaleNicotine and alcohol each can serve as the gateway to other drugs.ObjectiveThe current study was sought to determine if prior nicotine and alcohol exposure alters amphetamine reward and if age and dopaminergic neurotransmission are involved.MethodsMale and female adolescent and adult C57BL/6J mice were tested for baseline place preference, received six conditioning with saline/nicotine (0.25 mg/kg) twice daily followed by six conditioning with saline/ethanol (2 g/kg) in a counterbalance manner. Control mice were conditioned with saline/saline throughout. Finally, mice were conditioned with amphetamine (3 mg/kg) once in the nicotine-alcohol-paired chamber and then tested for CPP 24 h later. The following day, mice were challenged with amphetamine (1 mg/kg) and tested for CPP under a drugged state. Mice were then immediately euthanized, brain removed and nucleus accumbens isolated and processed for the expression of dopamine receptors and transporter, and glutamate receptors.ResultsWe observed a greater amphetamine-induced CPP in adolescent than adult mice but no change in state-dependent CPP between the two age groups. In contrast, amphetamine-induced CPP in mice with prior nicotine-alcohol exposure was greater in adult than adolescent mice under both drug-free and drugged states. The enhanced response in adult mice was associated with greater expression of dopamine-transporter, reduced D2 receptors, and increased D1 receptors with no changes in glutamate receptors.ConclusionsThese results suggest that prior nicotine and alcohol exposure differentially alters the rewarding action of amphetamine in adult and adolescent mice and alterations in dopaminergic neurotransmission may be involved in this phenotype.


2008 ◽  
pp. S111-S120
Author(s):  
P Mareš ◽  
H Kubová

Epileptic afterdischarges (ADs) elicited by electrical stimulation of sensorimotor cortical area were used as a model to study the role of neurotransmitter systems in cortical seizures in three age groups of developing rats. Drugs augmenting inhibition mediated by GABAA receptors were found to suppress ADs in all age groups, their activity was usually more marked in younger than in 25-day-old rat pups. Drugs potentiating GABAB receptors exhibit lower efficacy and more complicated developmental profile than GABAA-ergic drugs. Effects of an antagonist of GABAB receptor--marked prolongation of ADs in all three age groups--suggest an important role of GABAB receptors in arrest of cortical seizures. Drugs affecting glutamate receptors exhibit variable effects, usually better expressed in older animals than in 12-day-old ones. No specific role for ionotropic as well as metabotropic glutamate receptors could be predicted. Activation of adenosinergic inhibitory modulatory system also exhibited anticonvulsant action in the present model. All three neurotransmitter systems probably participate in mechanisms of generation, maintenance and arrest of cortical seizures.


1997 ◽  
Vol 9 (8) ◽  
pp. 815 ◽  
Author(s):  
J. L. Cook ◽  
C. L. Randall

These studies were designed to determine the effect of acute alcohol treatment on gestational length and to probe for a mechanism underlying alcohol-induced early onset of parturition (EOP) in mice. Experiment 1: alcohol increases the incidence of EOP. Pregnant C57BL/6J mice were given alcohol (0, 4, 5 or 6 g kg -1 , i.g.) on Gestational Day (GD) 10, 15, 16, 17 or 18. Deliveries were monitored every 6 h from GD 18. Results indicated that 6 g kg -1 alcohol treatment on GD 17 or 18 increased the incidence of EOP. Experiment 2: prostaglandins (PGs) play roles in parturition. The purpose of Experiment 2 was to determine whether PGs mediate alcohol-induced EOP in mice. The results indicated that pretreatment on GD 17 with aspirin, a prostaglandin synthesis inhibitor, prevented alcohol-induced EOP. These data suggest that alcohol-induced EOP in mice may be mediated by PGs. Experiment 3: PGs are influenced by alcohol and are triggers of labour. Experiment3 measured uterine PGs associated with the onset of alcohol-induced EOP in mice. Alcohol increased uterine PGE and PGF2a , with PGE levels higher than control before labour, and elevated PGF2a levels correlating with labour. Changes in gestational length have important implications for pregnancy outcome, as well as for normal fetal growth and development.


2007 ◽  
Vol 31 (12) ◽  
pp. 2001-2005 ◽  
Author(s):  
Mei Song ◽  
Xue-Yi Wang ◽  
Mei Zhao ◽  
Xiao-Yi Wang ◽  
Hai-Feng Zhai ◽  
...  

2000 ◽  
Vol 278 (2) ◽  
pp. R520-R528 ◽  
Author(s):  
Gina M. Whitney ◽  
Patricia J. Ohtake ◽  
Narong Simakajornboon ◽  
Ying-Dan Xue ◽  
David Gozal

The developmental role of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) glutamate receptors in respiratory regulation remains undefined. To study this issue, minute ventilation (V˙E) was measured in 5-, 10-, and 15-day-old intact freely behaving rat pups using whole body plethysmography during room air (RA), hypercapnic (5% CO2), and hypoxic (10% O2) conditions, both before and after administration of the non- N-methyl-d-aspartate (NMDA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide disodium (NBQX; 10 mg/kg ip). In all age groups,V˙E during RA was unaffected by NBQX, despite reductions in breathing frequency ( f) induced by increases in both inspiratory and expiratory duration. During hypoxia and hypercapnia, V˙Eincreases were similar in both NBQX and control conditions in all age groups. However, tidal volume was greater and f lower after NBQX. To determine if AMPA receptor-positive neurons are recruited during hypoxia, immunostaining for AMPA receptor (GluR2/3) and c -fos colabeling was performed in caudal brain stem sections after exposing rat pups at postnatal ages 2, 5, 10, and 20 days, and adult rats to room air or 10% O2 for 3 h. GluR2/3 expression increased with postnatal age in the nucleus of the solitary tract (NTS) and hypoglossal nucleus, whereas a biphasic pattern emerged for the nucleus ambiguus (NA). c -fos expression was enhanced by hypoxia at all postnatal ages in the NTS and NA and also demonstrated a clear maturational pattern. However, colocalization of GluR2/3 and c -fos was not affected by hypoxia. We conclude that AMPA glutamate receptor expression in the caudal brain stem is developmentally regulated. Furthermore, the role of non-NMDA receptors in respiratory control of conscious neonatal rats appears to be limited to modest, albeit significant, regulation of breathing pattern.


2013 ◽  
Vol 6 (2) ◽  
pp. 205-217 ◽  
Author(s):  
Vanessa Joosen

Compared to the attention that children's literature scholars have paid to the construction of childhood in children's literature and the role of adults as authors, mediators and readers of children's books, few researchers have made a systematic study of adults as characters in children's books. This article analyses the construction of adulthood in a selection of texts by the Dutch author and Astrid Lindgren Memorial Award winner Guus Kuijer and connects them with Elisabeth Young-Bruehl's recent concept of ‘childism’ – a form of prejudice targeted against children. Whereas Kuijer published a severe critique of adulthood in Het geminachte kind [The despised child] (1980), in his literary works he explores a variety of positions that adults can take towards children, with varying degrees of childist features. Such a systematic and comparative analysis of the way grown-ups are characterised in children's texts helps to shed light on a didactic potential that materialises in different adult subject positions. After all, not only literary and artistic aspects of children's literature may be aimed at the adult reader (as well as the child), but also the didactic aspect of children's books can cross over between different age groups.


2019 ◽  
Vol 106 (3) ◽  
pp. 250-260 ◽  
Author(s):  
DN Nandakumar ◽  
P Ramaswamy ◽  
C Prasad ◽  
D Srinivas ◽  
K Goswami

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.


2019 ◽  
Author(s):  
Bettina Moltrecht ◽  
Jessica Deighton ◽  
Praveetha Patalay ◽  
Julian Childs

Background: Research investigating the role of emotion regulation (ER) in the development and treatment of psychopathology has increased in recent years. Evidence suggests that an increased focus on ER in treatment can improve existing interventions. Most ER research has neglected young people, therefore the present meta-analysis summarizes the evidence for existing psychosocial intervention and their effectiveness to improve ER in youth. Methods: A systematic review and meta-analysis was conducted according to the PRISMA guidelines. Twenty-one randomized-control-trials (RCTs) assessed changes in ER following a psychological intervention in youth exhibiting various psychopathological symptoms.Results: We found moderate effect sizes for current interventions to decrease emotion dysregulation in youth (g=-.46) and small effect sizes to improve emotion regulation (g=0.36). Significant differences between studies including intervention components, ER measures and populations studied resulted in large heterogeneity. Conclusion: This is the first meta-analysis that summarizes the effectiveness for existing interventions to improve ER in youth. The results suggest that interventions can enhance ER in youth, and that these improvements correlate with improvements in psychopathology. More RCTs including larger sample sizes, different age groups and psychopathologies are needed to increase our understanding of what works for who and when.


There have been significant changes in the numbers, patterns, and circumstances of refugees and in the political landscape to support humanitarianism since the publication of the first edition of this collection. Like the first edition, this volume provides a multidisciplinary perspective on refugee health, tracing the health repercussions on individuals and populations from the drivers of forced mass movements of populations from situations of conflict and other disasters through to the process of resettlement in countries other than their countries of origin. Drawing on the expertise of academics, practitioners, and UN frontline experts, the collection covers three main aspects of refugee health: the concepts, definitions, and context from a human rights, humanitarianism, and social determinants of health perspective; the intersection of vulnerabilities across age groups and settings; and the ethical challenges for practitioners and researchers working with forcibly displaced populations seeking to resettle. The collection concludes with an analysis of the role of the media in shaping our perceptions of refugees and the impact on policy and access to care.


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