Extinction and drug‐induced reinstatement of cocaine seeking following self‐administration or conditioned place preference in adolescent and adult rats

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.

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Ibogaine Blocks Cue- and Drug-Induced Reinstatement of Conditioned Place Preference to Ethanol in Male Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2021.739012 ◽

2021 ◽

Vol 12 ◽

Author(s):

Gabrielle M. Henriques ◽

Alexia Anjos-Santos ◽

Isa R. S. Rodrigues ◽

Victor Nascimento-Rocha ◽

Henrique S. Reis ◽

...

Keyword(s):

Conditioned Place Preference ◽

Place Preference ◽

Free Access ◽

Repeated Treatment ◽

Male Mice ◽

Self Administration ◽

Drug Induced ◽

Exposure Test ◽

Therapeutic Properties ◽

Drug Free

Ibogaine is a psychedelic extracted from the plant Tabernanthe iboga Baill. (Apocynaceae), natural from Africa, and has been proposed as a potential treatment for substance use disorders. In animal models, ibogaine reduces ethanol self-administration. However, no study to date has investigated the effects of ibogaine on ethanol-induced conditioned place preference (CPP). The present study aimed to investigate the effects of repeated treatment with ibogaine on the reinstatement of CPP to ethanol in male mice. The rewarding effects of ethanol (1.8 g/kg, i. p.) or ibogaine (10 or 30 mg/kg, p. o.) were investigated using the CPP model. Furthermore, we evaluated the effects of repeated treatment with ibogaine (10 or 30 mg/kg, p. o.) on the reinstatement of ethanol-induced CPP. Reinstatement was evaluated under two conditions: 1) during a priming injection re-exposure test in which animals received a priming injection of ethanol and had free access to the CPP apparatus; 2) during a drug-free test conducted 24 h after a context-paired re-exposure, in which subjects received an injection of ethanol and were confined to the compartment previously conditioned to ethanol. Our results show that ethanol, but not ibogaine, induced CPP in mice. Treatment with ibogaine after conditioning with ethanol blocked the reinstatement of ethanol-induced CPP, both during a drug priming reinstatement test and during a drug-free test conducted after re-exposure to ethanol in the ethanol-paired compartment. Our findings add to the literature suggesting that psychedelics, in particular ibogaine, may have therapeutic properties for the treatment of alcohol use disorder at doses that do not have rewarding effects per se.

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Cebranopadol blocks the escalation of cocaine intake and conditioned reinstatement of cocaine seeking in rats

10.1101/140566 ◽

2017 ◽

Author(s):

Giordano de Guglielmo ◽

Alessandra Matzeu ◽

Jenni Kononoff ◽

Julia Mattioni ◽

Rémi Martin-Fardon ◽

...

Keyword(s):

Conditioned Place Preference ◽

Place Preference ◽

Orphanin Fq ◽

Self Administration ◽

Phase 3 ◽

Clinical Phase ◽

Cocaine Seeking ◽

Extended Access ◽

New Treatment ◽

Novel Strategy

AbstractCebranopadol is a novel agonist of nociceptin/orphanin FQ peptide (NOP) and opioid receptors with analgesic properties that is being evaluated in clinical Phase 2 and Phase 3 trials for the treatment of chronic and acute pain. Recent evidence indicates that the combination of opioid and NOP receptor agonism may be a new treatment strategy for cocaine addiction. We sought to extend these findings by examining the effects of cebranopadol on cocaine self-administration (0.5 mg/kg/infusion) and cocaine conditioned reinstatement in rats with extended access to cocaine. Oral administration of cebranopadol (0, 25, and 50 μg/kg) reversed the escalation of cocaine self-administration in rats that were given extended (6 h) access to cocaine, whereas it did not affect the self-administration of sweetened condensed milk (SCM). Cebranopadol induced conditioned place preference but did not affect locomotor activity during the conditioning sessions. Finally, cebranopadol blocked the conditioned reinstatement of cocaine seeking. These results show that oral cebranopadol treatment prevented addiction-like behaviors (i.e., the escalation of intake and reinstatement), suggesting that it may be a novel strategy for the treatment of cocaine use disorder. However, the conditioned place preference that was observed after cebranopadol administration suggests that this compound may have some intrinsic rewarding effects.

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CXCR4 antagonist Plerixafor attenuates cue and cue/drug induced relapse to cocaine seeking and expression and development of cocaine-induced conditioned place preference

Drug and Alcohol Dependence ◽

10.1016/j.drugalcdep.2016.08.286 ◽

2017 ◽

Vol 171 ◽

pp. e102

Author(s):

Jae K. Kim ◽

Scott Rawls

Keyword(s):

Conditioned Place Preference ◽

Place Preference ◽

Cxcr4 Antagonist ◽

Drug Induced ◽

Cocaine Seeking

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Odor Cues Effectively Reinstate Cocaine Self Administration, but Fail to Produce a Conditioned Place Preference

PsycEXTRA Dataset ◽

10.1037/e413792005-098 ◽

2000 ◽

Author(s):

Anthony S. Rauhut ◽

Michael T. Bardo

Keyword(s):

Conditioned Place Preference ◽

Place Preference ◽

Self Administration ◽

Odor Cues

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Cannabidiol Modulates the Motivational and Anxiety-Like Effects of 3,4-Methylenedioxypyrovalerone (MDPV) in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22158304 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8304

Author(s):

Laia Alegre-Zurano ◽

Raúl López-Arnau ◽

Miguel Á. Luján ◽

Jordi Camarasa ◽

Olga Valverde

Keyword(s):

Conditioned Place Preference ◽

Learning Task ◽

Place Preference ◽

Bath Salts ◽

Self Administration ◽

Preclinical Research ◽

Plus Maze ◽

Life Threatening ◽

Synthetic Cathinone ◽

High Responders

3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) and the most widespread and life-threatening synthetic cathinone of the “bath salts”. Preclinical research has proven the cocaine-like psychostimulant effects of MDPV and its potential for abuse. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid that has emerged as a new potential treatment for drug addiction. Here, we tested the effects of CBD (20 mg/kg) on MDPV (2 mg/kg)-induced conditioned place preference and MDPV (0.05 and 0.075 mg/kg/infusion) self-administration paradigms. In addition, we assessed the effects of the co-administration of CBD and MDPV (3 and 4 mg/kg) on anxiety-like behaviour using the elevated plus maze (EPM). CBD mitigated the MDPV-induced conditioned place preference. On the contrary, CBD administration throughout the MDPV (0.075 mg/kg/infusion) self-administration increased drug-seeking and taking behaviours, but only in the high-responders group of mice. Furthermore, CBD exerted anxiolytic-like effects, exclusively in MDPV-treated mice. Taken together, our results indicate that CBD modulation of MDPV-induced motivational responses in mice varies depending on the requirements of the learning task, resulting in a complex response. Therefore, further research attempting to decipher the behavioural and molecular interactions between CBD and MDPV is needed.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22052397 ◽

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.

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

Journal of Psychopharmacology ◽

10.1177/0269881118812098 ◽

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.

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