Influences of social reward experience on behavioral responses to drugs of abuse: Review of shared and divergent neural plasticity mechanisms for sexual reward and drugs of abuse

2017 ◽  
Vol 83 ◽  
pp. 356-372 ◽  
Author(s):  
Lauren N. Beloate ◽  
Lique M. Coolen
Keyword(s):  
Neural Plasticity ◽  
Drugs Of Abuse ◽  
Behavioral Responses ◽  
Social Reward

scholarly journals BDNF Is a Negative Modulator of Morphine Action

Science ◽  
2012 ◽  
Vol 338 (6103) ◽  
pp. 124-128 ◽  
Author(s):  
Ja Wook Koo ◽  
Michelle S. Mazei-Robison ◽  
Dipesh Chaudhury ◽  
Barbara Juarez ◽  
Quincey LaPlant ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Drugs Of Abuse ◽  
Suppressive Effect ◽  
Chronic Morphine ◽  
Target Region ◽  
Reward Circuitry ◽  
Stimulant Drugs ◽  
Insight Into ◽  
Major Target ◽  
Stimulation Of

Brain-derived neurotrophic factor (BDNF) is a key positive regulator of neural plasticity, promoting, for example, the actions of stimulant drugs of abuse such as cocaine. We discovered a surprising opposite role for BDNF in countering responses to chronic morphine exposure. The suppression of BDNF in the ventral tegmental area (VTA) enhanced the ability of morphine to increase dopamine (DA) neuron excitability and promote reward. In contrast, optical stimulation of VTA DA terminals in nucleus accumbens (NAc) completely reversed the suppressive effect of BDNF on morphine reward. Furthermore, we identified numerous genes in the NAc, a major target region of VTA DA neurons, whose regulation by BDNF in the context of chronic morphine exposure mediated this counteractive function. These findings provide insight into the molecular basis of morphine-induced neuroadaptations in the brain’s reward circuitry.

scholarly journals Loss of β-arrestin2 in D2 cells alters neuronal excitability in the nucleus accumbens and behavioral responses to psychostimulants and opioids

2019 ◽  
Author(s):  
Kirsten A. Porter-Stransky ◽  
Alyssa K. Petko ◽  
Saumya L. Karne ◽  
L. Cameron Liles ◽  
Nikhil M. Urs ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
G Protein ◽  
Conditioned Place Preference ◽  
Neuronal Excitability ◽  
Drugs Of Abuse ◽  
Behavioral Responses ◽  
Place Preference ◽  
Locomotor Sensitization ◽  
Drug Induced ◽  
G Protein Coupled

AbstractPsychostimulants and opioids increase dopamine (DA) neurotransmission, activating D1 and D2 G protein-coupled receptors. β-arrestin2 (βarr2) desensitizes and internalizes these receptors and initiates G protein-independent signaling. Previous work revealed that mice with a global or cell-specific knockout of βarr2 have altered responses to certain drugs; however, the effects of βarr2 on the excitability of medium spiny neurons (MSNs) and its role in mediating the rewarding effects of drugs of abuse are unknown. D1-Cre and D2-Cre transgenic mice were crossed with floxed βarr2 mice to eliminate βarr2 specifically in cells containing either D1 (D1βarr2-KO) or D2 (D2βarr2-KO) receptors. We used slice electrophysiology to characterize the role of βarr2 in modulating D1 and D2 nucleus accumbens MSN intrinsic excitability in response to DA and tested the locomotor-activating and rewarding effects of cocaine and morphine in these mice. We found that eliminating βarr2 attenuated the ability of DA to inhibit D2-MSNs but had little effect on the DA response of D1-MSNs. While D1βarr2-KO mice had mostly normal drug responses, D2βarr2-KO mice showed dose-dependent reductions in acute locomotor responses to cocaine and morphine, attenuated locomotor sensitization to cocaine, and blunted cocaine reward measured with conditioned place preference. Both D2βarr2-KO and D1βarr2-KO mice displayed an enhanced conditioned place preference for the highest dose of morphine. These results indicate that D2-derived βarr2 functionally contributes to the ability of DA to inhibit D2-MSNs and multiple behavioral responses to psychostimulants and opioids, while loss of βarr2 in D1 neurons has little impact on D1-MSN excitability or drug-induced behaviors.

scholarly journals Food Addiction, High-Glycemic-Index Carbohydrates, and Obesity

2018 ◽  
Vol 64 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Belinda Lennerz ◽  
Jochen K Lennerz
Keyword(s):  
Food Intake ◽  
Glycemic Index ◽  
Drugs Of Abuse ◽  
Behavioral Therapy ◽  
Food Addiction ◽  
Treatment Success ◽  
Behavioral Responses ◽  
Etiologic Factor ◽  
Environmental Interventions ◽  
High Glycemic Index

AbstractBACKGROUNDTreatment success in obesity remains low, and recently food addiction has been delineated as an underlying etiologic factor with therapeutic relevance. Specifically, current treatment focuses on reduced food intake and increase of physical activity, whereas interventions for addiction encompass behavioral therapy, abstinence, and environmental interventions such as taxation, restrictions on advertising, and regulation of school menus.CONTENTHere, we reviewed the pertinent literature on food addiction with a specific focus on the role of high-glycemic-index carbohydrates in triggering addictive symptoms. Three lines of evidence support the concept of food addiction: (a) behavioral responses to certain foods are similar to substances of abuse; (b) food intake regulation and addiction rely on similar neurobiological circuits; (c) individuals suffering from obesity or addiction show similar neurochemical- and brain activation patterns.High-glycemic-index carbohydrates elicit a rapid shift in blood glucose and insulin levels, akin to the pharmacokinetics of addictive substances. Similar to drugs of abuse, glucose and insulin signal to the mesolimbic system to modify dopamine concentration. Sugar elicits addiction-like craving, and self-reported problem foods are rich in high-glycemic-index carbohydrates. These properties make high-glycemic-index carbohydrates plausible triggers for food addiction.SUMMARYWe argue that food addiction is a plausible etiological factor contributing to the heterogeneous condition and phenotype of obesity. In at least a subset of vulnerable individuals, high-glycemic-index carbohydrates trigger addiction-like neurochemical and behavioral responses.

scholarly journals Is p38 MAPK Associated to Drugs of Abuse-Induced Abnormal Behaviors?

2020 ◽  
Vol 21 (14) ◽  
pp. 4833 ◽  
Author(s):  
Rana El Rawas ◽  
Inês M. Amaral ◽  
Alex Hofer
Keyword(s):  
P38 Mapk ◽  
Drugs Of Abuse ◽  
Behavioral Responses ◽  
Drug Effects ◽  
Therapeutic Interventions ◽  
Adverse Experiences ◽  
Mitogen Activated Protein ◽  
P38 Mapk Inhibitors ◽  
External Stresses ◽  
Mapk Inhibitors

The family members of the mitogen-activated protein kinases (MAPK) mediate a wide variety of cellular behaviors in response to extracellular stimuli. p38 MAPKs are key signaling molecules in cellular responses to external stresses and regulation of pro-inflammatory cytokines. Some studies have suggested that p38 MAPK in the region of the nucleus accumbens is involved in abnormal behavioral responses induced by drugs of abuse. In this review, we discuss the role of the p38 MAPK in the rewarding effects of drugs of abuse. We also summarize the implication of p38 MAPK in stress, anxiety, and depression. We opine that p38 MAPK activation is more closely associated to stress-induced aversive responses rather than drug effects per se, in particular cocaine. p38 MAPK is only involved in cocaine reward, predominantly when promoted by stress. Downstream substrates of p38 that may contribute to the p38 MAPK associated-behavioral responses are proposed. Finally, we suggest p38 MAPK inhibitors as possible therapeutic interventions against stress-related disorders by potentially increasing resilience against stress and addiction relapse induced by adverse experiences.

Domain-selective BET inhibition attenuates transcriptional and behavioral responses to cocaine

2021 ◽  
Author(s):  
Mandakini B Singh ◽  
Christopher J Babigian ◽  
Gregory C Sartor
Keyword(s):  
Drugs Of Abuse ◽  
Behavioral Responses ◽  
Transcriptional Response ◽  
Transcriptional Level ◽  
Behavioral Experiments ◽  
Bet Inhibitor ◽  
Domain Specific ◽  
Object Recognition Memory ◽  
Bet Inhibitors ◽  
Promising Treatment

Epigenetic pharmacotherapies have emerged as a promising treatment option for substance use disorder (SUD) due to their ability to reverse maladaptive transcriptional and behavioral responses to drugs of abuse. In particular, inhibitors of bromodomain and extra terminal domain (BET) reader proteins have been shown to reduce cocaine- and opioid-seeking behaviors in rodents. However, only pan-BET inhibitors, small molecules that bind to both bromodomains (BD1 and BD2) with all BET proteins, have been investigated in animal models of SUD. Given the potential side effects associated with pan-BET inhibitors, safer and more selective strategies are needed to advance BET therapeutics as a potential treatment for SUD. Here, we show that RVX-208, a clinically tested, BD2-selective BET inhibitor, dose-dependently reduced cocaine conditioned place preference in male mice, similar to the pan-BET inhibitor JQ1. In other behavioral experiments, RVX-208 treatment did not alter distance traveled, anxiety-like behavior, or novel object recognition memory. At the transcriptional level, RVX-208 attenuated the expression of multiple cocaine-induced genes in the nucleus accumbens. RVX-208 produced a distinct transcriptional response in stimulated primary neurons compared to JQ1 but had little effect on gene expression in non-stimulated neurons. Together, these data indicate that targeting domain-specific BET mechanisms may be an effective and safer strategy to reduce cocaine-induced neurobehavioral adaptations.

Disruption of PTEN coupling with 5-HT2C receptors suppresses behavioral responses induced by drugs of abuse

2006 ◽  
Vol 12 (3) ◽  
pp. 324-329 ◽  
Author(s):  
Shao-Ping Ji ◽  
Yun Zhang ◽  
Jamie Van Cleemput ◽  
Wen Jiang ◽  
Mingxia Liao ◽  
...  
Keyword(s):  
Drugs Of Abuse ◽  
Behavioral Responses
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