Cocaine self-administration specifically increases A2AR-D2R and D2R-sigma1R heteroreceptor complexes in the rat nucleus accumbens shell. Relevance for cocaine use disorder

2017 ◽  
Vol 155 ◽  
pp. 24-31 ◽  
Author(s):  
Dasiel O. Borroto-Escuela ◽  
Manuel Narváez ◽  
Karolina Wydra ◽  
Julia Pintsuk ◽  
Luca Pinton ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Nucleus Accumbens Shell ◽  
Self Administration ◽  
Cocaine Use ◽  
Heteroreceptor Complexes ◽  
Rat Nucleus Accumbens

scholarly journals OSU-6162, a Sigma1R Ligand in Low Doses, Can Further Increase the Effects of Cocaine Self-Administration on Accumbal D2R Heteroreceptor Complexes

2019 ◽  
Vol 37 (2) ◽  
pp. 433-444 ◽  
Author(s):  
Dasiel O. Borroto-Escuela ◽  
Wilber Romero-Fernandez ◽  
Karolina Wydra ◽  
Zilong Zhou ◽  
Agata Suder ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Ex Vivo ◽  
Proximity Ligation Assay ◽  
Low Doses ◽  
Nucleus Accumbens Shell ◽  
Self Administration ◽  
Proximity Ligation ◽  
Heteroreceptor Complexes ◽  
Behavioral Studies ◽  
A2ar Agonist

AbstractCocaine was previously shown to act at the Sigma1R which is a target for counteracting cocaine actions. It therefore becomes of interest to test if the monoamine stabilizer (–) OSU-6162 (OSU-6162) with a nanomolar affinity for the Sigma1R can acutely modulate in low doses the effects of cocaine self-administration. In behavioral studies, OSU-6162 (5 mg/kg, s.c.) did not significantly change the number of active lever pressing and cocaine infusions. However, a trend to reduce cocaine readouts was found after 3 days of treatment. In contrast, in maintenance of cocaine self-administration, the proximity ligation assay performed on brains from rats pretreated with OSU-6162 showed highly significant increases in the density of the D2R-Sigma1R heteroreceptor complexes in the shell of the nucleus accumbens versus OSU-6162 induced increases in this region of yoked saline rats. In cocaine self-administration, highly significant increases were also induced by OSU-6162 in the A2AR-D2R heteroreceptor complexes in the nucleus accumbens shell versus vehicle-treated rats. Furthermore, ex vivo, the A2AR agonist CGS21680 (100 nM) produced a marked and significant increase of the D2R Ki high values in the OSU-6162-treated versus vehicle-treated rats under maintenance of cocaine self-administration. These results indicate a substantial increase in the inhibitory allosteric A2AR-D2R interactions following cocaine self-administration upon activation by the A2AR agonist ex vivo. The current results indicate that OSU-6162 via its high affinity for the Sigma1R may increase the number of accumbal shell D2R-Sigma1R and A2AR-D2R heteroreceptor complexes associated with further increases in the antagonistic A2AR-D2R interactions in cocaine self-administration.

Role of neuropeptide neuromedin U in the nucleus accumbens shell in cocaine self-administration in male rats

2021 ◽  
Author(s):  
James M. Kasper ◽  
Ashley E. Smith ◽  
Sierra N. Miller ◽  
Ara ◽  
William K. Russell ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Male Rats ◽  
Nucleus Accumbens Shell ◽  
Self Administration

scholarly journals BDNF-TrkB controls cocaine-induced dendritic spines in rodent nucleus accumbens dissociated from increases in addictive behaviors

2017 ◽  
Vol 114 (35) ◽  
pp. 9469-9474 ◽  
Author(s):  
Ethan M. Anderson ◽  
Anne Marie Wissman ◽  
Joyce Chemplanikal ◽  
Nicole Buzin ◽  
Daniel Guzman ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Dendritic Spine ◽  
Morphological Changes ◽  
Dominant Negative ◽  
Addictive Behaviors ◽  
Spine Density ◽  
Nucleus Accumbens Shell ◽  
Self Administration ◽  
Dendritic Spine Density ◽  
Chronic Cocaine

Chronic cocaine use is associated with prominent morphological changes in nucleus accumbens shell (NACsh) neurons, including increases in dendritic spine density along with enhanced motivation for cocaine, but a functional relationship between these morphological and behavioral phenomena has not been shown. Here we show that brain-derived neurotrophic factor (BDNF) signaling through tyrosine kinase B (TrkB) receptors in NACsh neurons is necessary for cocaine-induced dendritic spine formation by using either localized TrkB knockout or viral-mediated expression of a dominant negative, kinase-dead TrkB mutant. Interestingly, augmenting wild-type TrkB expression after chronic cocaine self-administration reverses the sustained increase in dendritic spine density, an effect mediated by TrkB signaling pathways that converge on extracellular regulated kinase. Loss of TrkB function after cocaine self-administration, however, leaves spine density intact but markedly enhances the motivation for cocaine, an effect mediated by specific loss of TrkB signaling through phospholipase Cgamma1 (PLCγ1). Conversely, overexpression of PLCγ1 both reduces the motivation for cocaine and reverses dendritic spine density, suggesting a potential target for the treatment of addiction in chronic users. Together, these findings indicate that BDNF-TrkB signaling both mediates and reverses cocaine-induced increases in dendritic spine density in NACsh neurons, and these morphological changes are entirely dissociable from changes in addictive behavior.

scholarly journals Overexpression of the Histone Dimethyltransferase G9a in Nucleus Accumbens Shell Increases Cocaine Self-Administration, Stress-Induced Reinstatement, and Anxiety

2017 ◽  
Vol 38 (4) ◽  
pp. 803-813 ◽  
Author(s):  
Ethan M. Anderson ◽  
Erin B. Larson ◽  
Daniel Guzman ◽  
Anne Marie Wissman ◽  
Rachael L. Neve ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Nucleus Accumbens Shell ◽  
Self Administration

Segregation of caffeine reward and aversion in the rat nucleus accumbens shell versus core

2020 ◽  
Vol 52 (3) ◽  
pp. 3074-3086
Author(s):  
Mandy Yee ◽  
Geith Maal‐Bared ◽  
Ryan Ting‐A‐Kee ◽  
Michal Chwalek ◽  
Isabel Mackay‐Clackett ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Nucleus Accumbens Shell ◽  
Rat Nucleus Accumbens
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