scholarly journals Methamphetamine pre-exposure induces steeper escalation of methamphetamine self-administration with consequent alterations in hippocampal glutamate AMPA receptor mRNAs

2020 ◽  
Vol 889 ◽  
pp. 173732
Author(s):  
Michael R. Chojnacki ◽  
Subramaniam Jayanthi ◽  
Jean Lud Cadet
Author(s):  
Junshi Wang ◽  
King-Lun Li ◽  
Avani Shukla ◽  
Ania Beroun ◽  
Masago Ishikawa ◽  
...  

AbstractSynaptogenesis is essential in forming new neurocircuits during development, and this is mediated in part by astrocyte-released thrombospondins (TSPs) and activation of their neuronal receptor, α2δ-1. Here, we show that this developmental synaptogenic mechanism is utilized during cocaine experience to induce spinogenesis and the generation of AMPA receptor-silent glutamatergic synapses in the adult nucleus accumbens (NAc). Specifically, cocaine administration activates NAc astrocytes, and preventing this activation blocks cocaine-induced generation of silent synapses. Furthermore, knockout of TSP2, or pharmacological inhibition or viral-mediated knockdown of α2δ-1, prevents cocaine-induced generation of silent synapses. Moreover, disrupting TSP2-α2δ-1-mediated spinogenesis and silent synapse generation in the NAc occludes cue-induced cocaine seeking after withdrawal from cocaine self-administration and cue-induced reinstatement of cocaine seeking after drug extinction. These results establish that silent synapses are generated by an astrocyte-mediated synaptogenic mechanism in response to cocaine experience and embed critical cue-associated memory traces that promote cocaine relapse.


2013 ◽  
Vol 38 (9) ◽  
pp. 1789-1797 ◽  
Author(s):  
Anthony Purgianto ◽  
Andrew F Scheyer ◽  
Jessica A Loweth ◽  
Kerstin A Ford ◽  
Kuei Y Tseng ◽  
...  

1992 ◽  
Vol 15 ◽  
pp. 502B
Author(s):  
H. Tomita ◽  
M. Hikiji ◽  
Y. Fujiwara ◽  
K. Kashihara ◽  
J. Tomita ◽  
...  

2021 ◽  
Author(s):  
Sara Faccidomo ◽  
Elizabeth S Cogan ◽  
Olivia J. Hon ◽  
Jessica L Hoffman ◽  
Briana L Saunders ◽  
...  

AbstractAddiction is viewed as maladaptive glutamate-mediated neuroplasticity that is regulated, in part, by calcium-permeable AMPA receptor (CP-AMPAR) activity. However, the contribution of CP-AMPARs to alcohol-seeking behavior remains to be elucidated. We evaluated CP-AMPAR activity in the basolateral amygdala (BLA) as a potential target of alcohol that also regulates alcohol self-administration in C57BL/6J mice. Operant self-administration of sweetened alcohol increased spontaneous EPSC frequency in BLA neurons that project to the nucleus accumbens as compared to behavior-matched sucrose controls indicating an alcohol-specific upregulation of synaptic activity. Bath application of the CP-AMPAR antagonist NASPM decreased evoked EPSC amplitude only in alcohol self-administering mice indicating alcohol-induced synaptic insertion of CP-AMPARs in BLA projection neurons. Moreover, NASPM infusion in the BLA dose-dependently decreased the rate of operant alcohol self-administration providing direct evidence for CP-AMPAR regulation of alcohol reinforcement. Since most CP-AMPARs are GluA1-containing, we asked if alcohol alters the activation state of GluA1-containing AMPARs. Immunocytochemistry results showed elevated GluA1-S831 phosphorylation in the BLA of alcohol as compared to sucrose mice. To investigate mechanistic regulation of alcohol self-administration by GluA1-containing AMPARs, we evaluated the necessity of GluA1 trafficking using a TET-ON AAV encoding a dominant-negative GluA1 c-terminus (GluA1ct) that blocks activity-dependent synaptic delivery of native GluA1-containing AMPARs. GluA1ct expression in the BLA reduced alcohol self-administration with no effect on sucrose controls. These results show that CP-AMPAR activity and GluA1 trafficking in the BLA mechanistically regulate the reinforcing effects of sweetened alcohol. Pharmacotherapeutic targeting these mechanisms of maladaptive neuroplasticity may aid medical management of alcohol use disorder.


2016 ◽  
Vol 22 (3) ◽  
pp. 652-664 ◽  
Author(s):  
Reginald Cannady ◽  
Kristen R. Fisher ◽  
Caitlin Graham ◽  
Jesse Crayle ◽  
Joyce Besheer ◽  
...  

2012 ◽  
Vol 18 (1) ◽  
pp. 54-65 ◽  
Author(s):  
Reginald Cannady ◽  
Kristen R. Fisher ◽  
Brandon Durant ◽  
Joyce Besheer ◽  
Clyde W. Hodge

Methodology ◽  
2006 ◽  
Vol 2 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Joachim Gerich ◽  
Roland Lehner

Although ego-centered network data provide information that is limited in various ways as compared with full network data, an ego-centered design can be used without the need for a priori and researcher-defined network borders. Moreover, ego-centered network data can be obtained with traditional survey methods. However, due to the dynamic structure of the questionnaires involved, a great effort is required on the part of either respondents (with self-administration) or interviewers (with face-to-face interviews). As an alternative, we will show the advantages of using CASI (computer-assisted self-administered interview) methods for the collection of ego-centered network data as applied in a study on the role of social networks in substance use among college students.


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