scholarly journals Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval

2019 ◽  
Author(s):  
Koral Goltseker ◽  
Hen Handrus ◽  
Segev Barak
Keyword(s):  
Memory Retrieval ◽  
Lever Press ◽  
Water Flooding ◽  
Memory Reconsolidation ◽  
Place Conditioning ◽  
Self Administration ◽  
Conditioning Paradigm ◽  
Cocaine Seeking ◽  
Lever Pressing ◽  
Alcohol Seeking

AbstractRelapse to alcohol abuse is often caused by exposure to potent alcohol-associated cues. Therefore, disruption of the cue-alcohol memory can prevent relapse. It is believed that memories destabilize and become prone for updating upon their reactivation through retrieval, and then re-stabilize within 6 h during a “reconsolidation” process. We recently showed that relapse to cocaine seeking could be prevented by counterconditioning the cocaine-cues with aversive outcomes following cocaine-memory retrieval, in a place conditioning paradigm. However, to better model addiction-related behaviors, self-administration models are necessary. Here, we demonstrate that relapse to alcohol seeking can be prevented by aversive counterconditioning conducted during alcohol-memory reconsolidation, in conditioned place preference (CPP) and operant self-administration paradigms, in mice and rats, respectively. We found that the reinstatement of alcohol-CPP was abolished only when aversive counterconditioning with water-flooding was given shortly after alcohol-memory retrieval. Furthermore, rats trained to lever-press for alcohol showed decreased context-induced renewal of alcohol-seeking responding when the lever-pressing was counterconditioned with foot-shocks, shortly, but not 6 h, after memory retrieval. These results 0suggest that aversive counterconditioning can prevent relapse to alcohol seeking only when performed during alcohol-memory reconsolidation, presumably by updating, or replacing, the alcohol memory with aversive information. Also, we found that aversive counterconditioning preceded by alcohol-memory retrieval was characterized by upregulation of brain-derived neurotrophic factor (Bdnf) mRNA expression in the medial prefrontal cortex, suggesting that Bdnf plays a role in the memory updating process.

scholarly journals Basolateral amygdala CB1 receptors modulate HPA axis activation and context-cocaine memory strength during reconsolidation

2020 ◽  
Author(s):  
Jessica A. Higginbotham ◽  
Nicole M. Jones ◽  
Rong Wang ◽  
Ryan J. McLaughlin ◽  
Rita A. Fuchs
Keyword(s):  
Memory Retrieval ◽  
Basolateral Amygdala ◽  
Memory Reconsolidation ◽  
Long Term Memory ◽  
Memory Strength ◽  
Corticosterone Concentration ◽  
Cannabinoid Type 1 Receptor ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
The Impact

ABSTRACTRe-exposure to a cocaine-associated context triggers craving and relapse through the retrieval of salient context-drug memories. Upon retrieval, context-drug memories become labile and temporarily sensitive to modification before they are reconsolidated into long-term memory stores. Cannabinoid type 1 receptor (CB1R) signaling is necessary for cocaine-memory reconsolidation and associated glutamatergic plasticity in the basolateral amygdala (BLA); however, it remains unclear whether CB1Rs in the BLA mediate this phenomenon. To investigate this question, we examined whether CB1R antagonist or agonist administration into the BLA immediately after cocaine-memory retrieval (i.e., during memory reconsolidation) alters cocaine-memory strength and subsequent drug context-induced cocaine-seeking behavior in an instrumental rodent model of cocaine relapse. Intra-BLA administration of the CB1R antagonist, AM251 (0.3 µg/hemisphere) – during, but not after, memory reconsolidation – increased drug context-induced cocaine-seeking behavior three days later, while the CB1R agonist, WIN55,212-2 (0.5 µg/hemisphere) failed to alter this behavior. Furthermore, AM251 administration into the posterior caudate putamen (anatomical control region) during memory reconsolidation did not alter subsequent context-induced cocaine-seeking behavior. In a follow-up experiment, cocaine-memory retrieval elicited robust hypothalamic-pituitary-adrenal axis activation, as indicated by an increase in blood serum corticosterone concentration, and this response was selectively extended by intra-BLA AM251 administration during the putative time of memory reconsolidation relative to all control conditions. Together, these findings suggest that CB1R populations in the BLA gate memory strength or interfere with memory maintenance, possibly by diminishing the impact of cue-induced arousal on the integrity of the reconsolidating memory trace or on the efficiency of the memory reconsolidation process.

Impulsivity and Drug Addiction: A Neurobiological Perspective

2012 ◽  
Author(s):  
Trevor Robbins
Keyword(s):  
Drug Addiction ◽  
Conceptual Analysis ◽  
Animal Studies ◽  
Reaction Time Task ◽  
Compulsive Behavior ◽  
Self Administration ◽  
Detailed Characterization ◽  
Cocaine Seeking ◽  
Serial Reaction

A conceptual analysis of the impulsivity construct in behavioral and neurobiological terms is followed by an analysis of its causal role in certain forms of drug addiction in both human and animal studies. The main focus of this chapter is on a rat model of impulsivity based on premature responding in the five-choice serial reaction time task and a more detailed characterization of this phenotype in neurobehavioral, neurochemical, and genetic terms. Evidence is surveyed that high impulsivity on this task is associated with the escalation subsequently of cocaine self-administration behavior and also with a tendency toward compulsive cocaine seeking. Novelty reactivity, by contrast, is associated with the enhanced acquisition of self-administration, but not with the escalation of intravenous self-administration of cocaine or the development of compulsive behavior associated with cocaine seeking. These results indicate that the vulnerability to stimulant addiction may depend on different factors, as expressed through distinct presumed endophenotypes. These observations help us further to dissociate various aspects of the impulsivity construct in neural as well as behavioral terms.

scholarly journals Cannabinoid-Induced Conditioned Place Preference, Intravenous Self-Administration, and Behavioral Stimulation Influenced by Ghrelin Receptor Antagonism in Rats

2021 ◽  
Vol 22 (5) ◽  
pp. 2397
Author(s):  
Chrysostomos Charalambous ◽  
Tereza Havlickova ◽  
Marek Lapka ◽  
Nina Puskina ◽  
Romana Šlamberová ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Fixed Ratio ◽  
Place Preference ◽  
Self Administration ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Addiction Therapy ◽  
Significant Efficacy ◽  
Lever Pressing

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2 self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 120-min IVSA sessions under a fixed ratio FR1, which significantly reduced the number of the active lever-pressing, the number of infusions, and the cannabinoid intake. Pretreatment with JMV2959 suggested reduction of the WIN55,212-2-seeking/relapse-like behavior tested in rats on the twelfth day of the forced abstinence period. On the contrary, pretreatment with ghrelin significantly increased the cannabinoid IVSA as well as enhanced the relapse-like behavior. Co-administration of ghrelin with JMV2959 abolished/reduced the significant efficacy of the GHS-R1A antagonist in the cannabinoid IVSA. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of THC-induced CPP. The THC-CPP development was reduced after the simultaneous administration of JMV2959 with THC during conditioning. JMV2959 also significantly reduced the THC-induced behavioral stimulation in the LABORAS cage. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of cannabinoids.

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 Prolonged Withdrawal from Escalated Oxycodone is Associated with Increased Expression of Glutamate Receptors in the Rat Hippocampus

2020 ◽  
Author(s):  
Aaron J Salisbury ◽  
Christopher A Blackwood ◽  
Jean Lud Cadet
Keyword(s):  
Glutamate Receptors ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Opioid Use Disorder ◽  
Mrna Levels ◽  
Opioid Use ◽  
Self Administration ◽  
Lever Pressing ◽  
Polymerase Chain ◽  
Long Access

People suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 hours and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction (qPCR) analyses. Rats, given long-access (9 hours per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 hours per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression of GluA1-3 and GluN2a-c subunits as well as Grm3, Grm5, Grm6 and Grm8 subtypes of glutamate receptors after 31 days but not after 2 hours of stopping the SA experiment. Changes in GluA1-3, Grm6, and Grm8 mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.

scholarly journals Stress vulnerability promotes an alcohol prone phenotype in a preclinical model of sustained depression

2018 ◽  
Author(s):  
Danai Riga ◽  
Leanne JM Schmitz ◽  
Yvar van Mourik ◽  
Witte JG Hoogendijk ◽  
Taco J De Vries ◽  
...  
Keyword(s):  
Social Defeat ◽  
Preclinical Model ◽  
Self Administration ◽  
Depression Vulnerability ◽  
Stress Vulnerability ◽  
The Social ◽  
Depression Proneness ◽  
Male Wistar Rats ◽  
Alcohol Seeking

AbstractMajor depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat-induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (5 episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction and cue-induced reinstatement of alcohol-seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, excessive motivation to acquire alcohol, persistent alcohol-seeking despite alcohol unavailability, extinction resistance and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol-seeking and -taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.

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.

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