Effects of selective dopamine D1 or D2 receptor blockade within nucleus accumbens subregions on ingestive behavior and associated motor activity

Amylin, a calcitonin gene-related peptide-like peptide coreleased with insulin, exerts anorexic effects on central administration. Because previous studies revealed dense amylin binding in the nucleus accumbens (Acb), we investigated the behavioral effects of amylin infusions (10, 30, and 100 ng/side) into Acb subregions. Intra-Acb shell amylin infusions decreased ambulation, rearing, feeding, and drinking in either food-deprived rats or water-deprived rats; motor activity was affected more potently than ingestive behavior. Moreover, intra-Acb shell amylin reduced motor activity in nondeprived rats tested in the absence of food or water, indicating that the expression of amylin's effects is independent of drive or proximal incentives. Intra-Acb core amylin infusions in water-deprived rats also decreased ambulation and water intake, although anterior Acb placements were associated with smaller motor effects, regardless of Acb subregion. In contrast to amylin's effects, intra-Acb shell infusions of orexin-A (50, 100, and 500 ng/side) had no effects on motor activity, feeding, or drinking. Hence the Acb may be a target for behavioral regulation by satiety-related peptides like amylin.

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Intact discrimination reversal learning but slowed responding to reward-predictive cues after dopamine D1 and D2 receptor blockade in the nucleus accumbens of rats

Psychopharmacology ◽

10.1007/s00213-006-0532-y ◽

2006 ◽

Vol 191 (3) ◽

pp. 551-566 ◽

Cited By ~ 24

Author(s):

Carsten Calaminus ◽

Wolfgang Hauber

Keyword(s):

Nucleus Accumbens ◽

Reversal Learning ◽

D2 Receptor ◽

Discrimination Reversal ◽

Receptor Blockade

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Fluctuations in hallucinatory experiences within a day in relation to dopamine D2 receptor blockade with antipsychotics in patients with schizophrenia

10.26226/morressier.5b68175fb56e9b005965c627 ◽

2018 ◽

Author(s):

Teruki Koizumi

Keyword(s):

Dopamine D2 Receptor ◽

D2 Receptor ◽

Receptor Blockade ◽

Dopamine D2

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Faculty Opinions recommendation of Acute D2 receptor blockade induces rapid, reversible remodeling in human cortical-striatal circuits.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.5236956.5177054 ◽

2010 ◽

Author(s):

Ahmad Hariri ◽

Ryan Bogdan

Keyword(s):

D2 Receptor ◽

Receptor Blockade

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Dopaminylation in Psychostimulant use Disorder Protects Against Psychostimulant Seeking Behavior by Normalizing Nucleus Accumbens (NAc) Dopamine Expression

Current Psychopharmacologye ◽

10.2174/2211556009666210108112737 ◽

2021 ◽

Vol 09 ◽

Author(s):

Kenneth Blum ◽

Mark S Gold ◽

Jean L. Cadet ◽

David Baron ◽

Abdalla Bowirrat ◽

...

Keyword(s):

Nucleus Accumbens ◽

Histone H3 ◽

D2 Receptor ◽

Reward Processing ◽

Allelic Polymorphism ◽

Cocaine Withdrawal ◽

Src Signaling ◽

Chronic Cocaine ◽

Cocaine Seeking ◽

Seeking Behavior

Background: Repeated cocaine administration changes histone acetylation and methylation on Lys residues and Deoxyribonucleic acid (DNA) within the nucleus accumbens (NAc). Recently Nestler’s group explored histone Arg (R) methylation in reward processing models. Damez-Werno et al. (2016) reported that during investigator and selfadministration experiments, the histone mark protein-R-methyltransferase-6 (PRMT6) and asymmetric dimethylation of R2 on histone H3 (H3R2me2a) decreased in the rodent and cocaine-dependent human NAc. Overexpression of PRMT6 in D2-MSNs in all NAc neurons increased cocaine seeking, whereas PRMT6 overexpression in D1-MSNs protects against cocaine-seeking. Hypothesis: Hypothesizing that dopaminylation (H3R2me2a binding) occurs in psychostimulant use disorder (PSU), and the binding inhibitor Srcin1, like the major DRD2 A2 allelic polymorphism, protects against psychostimulant seeking behavior by normalizing nucleus accumbens (NAc) dopamine expression. Discussion: Numerous publications confirmed the association between the DRD2 Taq A1 allele (30-40 lower D2 receptor numbers) and severe cocaine dependence. Lepack et al. (2020) found that acute cocaine increases dopamine in NAc synapses, results in histone H3 glutamine 5 dopaminylation (H3Q5dop), and consequent inhibition of D2 expression. The inhibition increases with chronic cocaine use and accompanies cocaine withdrawal. They also found that the Src kinase sig-naling inhibitor 1 (Srcin1 or p140CAP) during cocaine withdrawal reduced H3R2me2a binding. Consequently, this inhibited dopaminylation induced a “homeostatic brake.” Conclusion: The decrease in Src signaling in NAc D2-MSNs, like the DRD2 Taq A2 allele, a well-known genetic mechanism protective against SUD normalized nucleus accumbens (NAc) dopamine expression and decreased cocaine reward and motivation to self-administer cocaine. The Srcin1 may be an important therapeutic target.

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The Adenosine A2A Receptor Activation in Nucleus Accumbens Suppress Cue-Induced Reinstatement of Propofol Self-administration in Rats

Neurochemical Research ◽

10.1007/s11064-021-03238-9 ◽

2021 ◽

Author(s):

Zhanglei Dong ◽

Bingwu Huang ◽

Chenchen Jiang ◽

Jiangfan Chen ◽

Han Lin ◽

...

Keyword(s):

Nucleus Accumbens ◽

D2 Receptor ◽

Fixed Ratio ◽

Receptor Activation ◽

Addictive Behaviors ◽

Self Administration ◽

A2a Receptors ◽

Mediated Effects ◽

Seeking Behavior ◽

Adenosine A2a

AbstractPropofol has shown strong addictive properties in rats and humans. Adenosine A2A receptors (A2AR) in the nucleus accumbens (NAc) modulate dopamine signal and addictive behaviors such as cocaine- and amphetamine-induced self-administration. However, whether A2AR can modulate propofol addiction remains unknown. AAV-shA2AR was intra-NAc injected 3 weeks before the propofol self-administration training to test the impacts of NAc A2AR on establishing the self-administration model with fixed ratio 1 (FR1) schedule. Thereafter, the rats were withdrawal from propofol for 14 days and tested cue-induced reinstatement of propofol seeking behavior on day 15. The propofol withdrawal rats received one of the doses of CGS21680 (A2AR agonist, 2.5–10.0 ng/site), MSX-3 (A2AR antagonist, 5.0–20.0 μg/site) or eticlopride (D2 receptor (D2R) antagonist, 0.75–3.0 μg/site) or vehicle via intra-NAc injection before relapse behavior test. The numbers of active and inactive nose-poke response were recorded. Focal knockdown A2AR by shA2AR did not affect the acquisition of propofol self-administration behavior, but enhance cue-induced reinstatement of propofol self-administration compared with the AAV-shCTRLgroup. Pharmacological activation of the A2AR by CGS21680 (≥ 5.0 ng/site) attenuated cue-induced reinstatement of propofol self-administration behavior. Similarly, pharmacological blockade of D2R by eticlopride (0.75–3.0 μg/site) attenuated propofol seeking behavior. These effects were reversed by the administration of MSX-3 (5.0–20.0 μg/site). The A2AR- and D2R-mediated effects on propofol relapse were not confounded by the learning process, and motor activity as the sucrose self-administration and locomotor activity were not affected by all the treatments. This study provides genetic and pharmacological evidence that NAc A2AR activation suppresses cue-induced propofol relapse in rats, possibly by interacting with D2R.

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