scholarly journals Extinction vs. Abstinence: A Review of the Molecular and Circuit Consequences of Different Post-Cocaine Experiences

2021 ◽  
Vol 22 (11) ◽  
pp. 6113
Author(s):  
Marek Schwendt ◽  
Lori A. Knackstedt
Keyword(s):  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Dorsal Striatum ◽  
Extinction Training ◽  
Face Validity ◽  
Self Administration ◽  
Cocaine Seeking ◽  
Glutamate Receptor Antagonists ◽  
The Impact ◽  
Abstinence Period

The intravenous cocaine self-administration model is widely used to characterize the neurobiology of cocaine seeking. When studies are aimed at understanding relapse to cocaine-seeking, a post-cocaine abstinence period is imposed, followed by “relapse” tests to assess the ability of drug-related stimuli (“primes”) to evoke the resumption of the instrumental response previously made to obtain cocaine. Here, we review the literature on the impact of post-cocaine abstinence procedures on neurobiology, finding that the prelimbic and infralimbic regions of the prefrontal cortex are recruited by extinction training, and are not part of the relapse circuitry when extinction training does not occur. Pairing cocaine infusions with discrete cues recruits the involvement of the NA, which together with the dorsal striatum, is a key part of the relapse circuit regardless of abstinence procedures. Differences in molecular adaptations in the NA core include increased expression of GluN1 and glutamate receptor signaling partners after extinction training. AMPA receptors and glutamate transporters are similarly affected by abstinence and extinction. Glutamate receptor antagonists show efficacy at reducing relapse following extinction and abstinence, with a modest increase in efficacy of compounds that restore glutamate homeostasis after extinction training. Imaging studies in humans reveal cocaine-induced adaptations that are similar to those produced after extinction training. Thus, while instrumental extinction training does not have face validity, its use does not produce adaptations distinct from human cocaine users.

scholarly journals Maternal Diet Influences the Reinstatement of Cocaine-Seeking Behavior and the Expression of Melanocortin-4 Receptors in Female Offspring of Rats

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1462
Author(s):  
Dawid Gawliński ◽  
Kinga Gawlińska ◽  
Małgorzata Frankowska ◽  
Małgorzata Filip
Keyword(s):  
Maternal Diet ◽  
Dorsal Striatum ◽  
Brain Structures ◽  
Female Offspring ◽  
Self Administration ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
Pregnancy And Lactation ◽  
The Impact ◽  
Cocaine Reward

Recent studies have emphasized the role of the maternal diet in the development of mental disorders in offspring. Substance use disorder is a major global health and economic burden. Therefore, the search for predisposing factors for the development of this disease can contribute to reducing the health and social damage associated with addiction. In this study, we focused on the impact of the maternal diet on changes in melanocortin-4 (MC-4) receptors as well as on behavioral changes related to cocaine addiction. Rat dams consumed a high-fat diet (HFD), high-sugar diet (HSD, rich in sucrose), or mixed diet (MD) during pregnancy and lactation. Using an intravenous cocaine self-administration model, the susceptibility of female offspring to cocaine reward and cocaine-seeking propensities was evaluated. In addition, the level of MC-4 receptors in the rat brain structures related to cocaine reward and relapse was assessed. Modified maternal diets did not affect cocaine self-administration in offspring. However, the maternal HSD enhanced cocaine-seeking behavior in female offspring. In addition, we observed that the maternal HSD and MD led to increased expression of MC-4 receptors in the nucleus accumbens, while increased MC-4 receptor levels in the dorsal striatum were observed after exposure to the maternal HSD and HFD. Taken together, it can be concluded that a maternal HSD is an important factor that triggers cocaine-seeking behavior in female offspring and the expression of MC-4 receptors.

scholarly journals Effects of adolescent caffeine consumption on cocaine self-administration and reinstatement of cocaine seeking

2018 ◽  
Vol 33 (1) ◽  
pp. 132-144
Author(s):  
Tracey A Larson ◽  
Casey E O’Neill ◽  
Michaela P Palumbo ◽  
Ryan K Bachtell
Keyword(s):  
Dose Response ◽  
Extinction Training ◽  
Schedules Of Reinforcement ◽  
Sprague Dawley ◽  
Self Administration ◽  
Caffeine Consumption ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Cocaine Seeking ◽  
Administration Procedure

Background: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. Aim: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. Methods: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62–82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. Results: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. Conclusions: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.

scholarly journals Extinction Training after Cocaine Self-Administration Induces Glutamatergic Plasticity to Inhibit Cocaine Seeking

2010 ◽  
Vol 30 (23) ◽  
pp. 7984-7992 ◽  
Author(s):  
L. A. Knackstedt ◽  
K. Moussawi ◽  
R. Lalumiere ◽  
M. Schwendt ◽  
M. Klugmann ◽  
...  
Keyword(s):  
Extinction Training ◽  
Self Administration ◽  
Cocaine Seeking

scholarly journals Addictive behaviour in experimental animals: prospects for translation

2018 ◽  
Vol 373 (1742) ◽  
pp. 20170027 ◽  
Author(s):  
Barry J. Everitt ◽  
Chiara Giuliano ◽  
David Belin
Keyword(s):  
Molecular Mechanisms ◽  
Animal Experiments ◽  
Neural Circuitry ◽  
Clinical State ◽  
Self Administration ◽  
Addictive Behaviour ◽  
Cocaine Seeking ◽  
New Treatments ◽  
The Impact ◽  
Chronic Use

Since the introduction of intravenous drug self-administration methodology over 50 years ago, experimental investigation of addictive behaviour has delivered an enormous body of data on the neural, psychological and molecular mechanisms of drug reward and reinforcement and the neuroadaptations to chronic use. Whether or not these behavioural and molecular studies are viewed as modelling the underpinnings of addiction in humans, the discussion presented here highlights two areas—the impact of drug-associated conditioned stimuli—or drug cues—on drug seeking and relapse, and compulsive cocaine seeking. The degree to which these findings translate to the clinical state of addiction is considered in terms of the underlying neural circuitry and also the ways in which this understanding has helped develop new treatments for addiction. The psychological and neural mechanisms underlying drug memory reconsolidation and extinction established in animal experiments show particular promise in delivering new treatments for relapse prevention to the clinic.This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.

scholarly journals Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Dasiel O. Borroto-Escuela ◽  
Karolina Wydra ◽  
Julia Pintsuk ◽  
Manuel Narvaez ◽  
Fidel Corrales ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Neural Plasticity ◽  
Molecular Basis ◽  
Dorsal Striatum ◽  
Self Administration ◽  
Heteroreceptor Complexes ◽  
Gaba Neurons ◽  
Cocaine Seeking ◽  
Receptor Interactions ◽  
Reward Motivation

Our hypothesis is that allosteric receptor-receptor interactions in homo- and heteroreceptor complexes may form the molecular basis of learning and memory. This principle is illustrated by showing how cocaine abuse can alter the adenosine A2AR-dopamine D2R heterocomplexes and their receptor-receptor interactions and hereby induce neural plasticity in the basal ganglia. Studies with A2AR ligands using cocaine self-administration procedures indicate that antagonistic allosteric A2AR-D2R heterocomplexes of the ventral striatopallidal GABA antireward pathway play a significant role in reducing cocaine induced reward, motivation, and cocaine seeking. Anticocaine actions of A2AR agonists can also be produced at A2AR homocomplexes in these antireward neurons, actions in which are independent of D2R signaling. At the A2AR-D2R heterocomplex, they are dependent on the strength of the antagonistic allosteric A2AR-D2R interaction and the number of A2AR-D2R and A2AR-D2R-sigma1R heterocomplexes present in the ventral striatopallidal GABA neurons. It involves a differential cocaine-induced increase in sigma1Rs in the ventral versus the dorsal striatum. In contrast, the allosteric brake on the D2R protomer signaling in the A2AR-D2R heterocomplex of the dorsal striatopallidal GABA neurons is lost upon cocaine self-administration. This is potentially due to differences in composition and allosteric plasticity of these complexes versus those in the ventral striatopallidal neurons.

G9a/GLP Complex Acts as a Bidirectional Switch to Regulate Metabotropic Glutamate Receptor-Dependent Plasticity in Hippocampal CA1 Pyramidal Neurons

2018 ◽  
Vol 29 (7) ◽  
pp. 2932-2946 ◽  
Author(s):  
Mahima Sharma ◽  
Sreedharan Sajikumar
Keyword(s):  
Glutamate Receptor ◽  
Epigenetic Regulation ◽  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Metabotropic Glutamate ◽  
The Impact

Abstract Metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) is conventionally considered to be solely dependent on local protein synthesis. Given the impact of epigenetics on memory, the intriguing question is whether epigenetic regulation influences mGluR-LTD as well. G9a/GLP histone lysine methyltransferase complex is crucial for brain development and goal-directed learning as well as for drug-addiction. In this study, we analyzed whether the epigenetic regulation by G9a/GLP complex affects mGluR-LTD in CA1 hippocampal pyramidal neurons of 5–7 weeks old male Wistar rats. In hippocampal slices with intact CA1 dendritic regions, inhibition of G9a/GLP activity abolished mGluR-LTD. The inhibition of this complex upregulated the expression of plasticity proteins like PKMζ, which mediated the prevention of mGluR-LTD expression by regulating the NSF-GluA2-mediated trafficking of AMPA receptors towards the postsynaptic site. G9a/GLP inhibition during the induction of mGluR-LTD also downregulated the protein levels of phosphorylated-GluA2 and Arc. Interestingly, G9a/GLP inhibition could not impede the mGluR-LTD when the cell-body was severed. Our study highlights the role of G9a/GLP complex in intact neuronal network as a bidirectional switch; when turned on, it facilitates the expression of mGluR-LTD, and when turned off, it promotes the expression of long-term potentiation.

Sign in / Sign up

Export Citation Format

Share Document