scholarly journals Nicotine and Opioid Polysubstance Abuse: Enhancement of opioid self-administration by systemic nicotine and modulation of opioid-associated memories by insular nicotine

2020 ◽  
Author(s):  
Gregory C Loney ◽  
Christopher P King ◽  
Paul J Meyer
Keyword(s):  
Insular Cortex ◽  
Place Preference ◽  
Treatment Programs ◽  
Opioid Use ◽  
Self Administration ◽  
Taste Avoidance ◽  
Contextual Conditioning ◽  
Nicotine Pretreatment ◽  
Polysubstance Abuse ◽  
Higher Doses

AbstractConcurrent nicotine use is associated with increased liability for the development and exacerbation of opioid-use disorders. Habitual use of nicotine containing products increases propensity to misuse prescription opioids and its prevalence is substantially increased in individuals currently involved in opioid-treatment programs. Nicotine enhances self-administration of many classes of drugs in rodents, though evidence for direct effects on opioids is lacking. We sought to measure the effects of nicotine pretreatment on the reinforcing efficacy of opioids in both self-administration and contextual conditioning paradigms. First, we measured the effect of systemic nicotine pretreatment on self-administration of two opioids. Additionally, we measured the degree to which systemic nicotine pretreatment impacts the formation of morphine-associated contextual memories in conditioned taste avoidance and place preference paradigms. Given the involvement of the insula in the maintenance of substance abuse, its importance in nicotine addiction, and findings that insular inactivation impairs contextual drug conditioning, we examined whether nicotine administered directly to the insula could recapitulate the effects of systemic nicotine. We demonstrate that systemic nicotine pretreatment significantly enhances opioid self-administration and alters contextual conditioning. Furthermore, intra-insula nicotine similarly altered morphine contextual conditioning by blocking the formation of taste avoidance at all three morphine doses tested (5.0, 10, & 20 mg/kg), while shifting the dose-response curve of morphine in the place preference paradigm rightward. In conclusion, these data demonstrate that nicotine facilitates opioid intake and is partly acting within the insular cortex to obfuscate aversive opiate memories while potentiating approach to morphine-associated stimuli at higher doses.

scholarly journals Systemic nicotine enhances opioid self-administration and modulates the formation of opioid-associated memories partly through actions within the insular cortex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gregory C. Loney ◽  
Christopher P. King ◽  
Paul J. Meyer
Keyword(s):  
Insular Cortex ◽  
Place Preference ◽  
Treatment Programs ◽  
Prescription Opioids ◽  
Direct Effects ◽  
Self Administration ◽  
Taste Avoidance ◽  
Contextual Conditioning ◽  
Nicotine Pretreatment ◽  
Higher Doses

AbstractHabitual use of nicotine containing products increases propensity to misuse prescription opioids and its prevalence is substantially increased in individuals currently involved in opioid-treatment programs. Nicotine enhances self-administration of many classes of drugs in rodents, though evidence for direct effects on opioids is lacking. We sought to measure the effects of nicotine pretreatment on the reinforcing efficacy of opioids in both self-administration and contextual conditioning paradigms. First, we measured the effect of systemic nicotine pretreatment on self-administration of two opioids. Additionally, we measured the degree to which systemic nicotine pretreatment impacts the formation of morphine-associated contextual memories in conditioned taste avoidance and place preference paradigms. Given the involvement of the insula in the maintenance of substance abuse, its importance in nicotine addiction, and findings that insular inactivation impairs contextual drug conditioning, we examined whether nicotine administered directly to the insula could recapitulate the effects of systemic nicotine. We demonstrate that systemic nicotine pretreatment significantly enhances opioid self-administration and alters contextual conditioning. Furthermore, intra-insula nicotine similarly altered morphine contextual conditioning by blocking the formation of taste avoidance at all three morphine doses tested (5.0, 10, and 20 mg/kg), while shifting the dose–response curve of morphine in the place preference paradigm rightward. In conclusion, these data demonstrate that nicotine facilitates opioid intake and is partly acting within the insular cortex to obfuscate aversive opiate memories while potentiating approach to morphine-associated stimuli at higher doses.

scholarly journals Ketamine blocks morphine-induced conditioned place preference and anxiety-like behaviors in mice

2020 ◽  
Author(s):  
Greer McKendrick ◽  
Hannah Garrett ◽  
Holly E. Jones ◽  
Dillon S. McDevitt ◽  
Sonakshi Sharma ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Elevated Plus Maze ◽  
Opioid Use Disorder ◽  
Place Preference ◽  
Affective States ◽  
Opioid Use ◽  
Self Administration ◽  
Plus Maze ◽  
Negative Affective States ◽  
Motivated Behaviors

AbstractPatients suffering from opioid use disorder often relapse during periods of abstinence, which is posited to be caused by negative affective states that drive motivated behaviors. Here, we explored whether conditioning mice with morphine in a CPP training paradigm evoked anxietylike behavior during morphine abstinence. To do this, mice were conditioned with morphine (10 mg/kg, i.p.) for five days. 24 h following conditioning, anxiety levels were tested by measuring time in the open arms of the elevated plus maze. The next day, mice were placed in the three compartment chamber to measure morphine-induced conditioned place preference (CPP). Our results show that following morphine conditioning, mice spent significantly less time in the open arm of the elevated plus maze and expressed robust morphine CPP on CPP test day. Furthermore, we found that an acute treatment with (R,S)-ketamine (10 mg/kg, i.p.), a medication demonstrating promise for preventing anxiety-related phenotypes, 30 min. prior to testing on post conditioning day 1, increased time spent in the open arm of the elevated plus maze in saline- and morphine-conditioned mice. Additionally, we found that a second injection of ketamine 30 min. prior to CPP tests on post conditioning day 2 prevented morphine-induced CPP, which lasted for up to 28 d post conditioning. Furthermore, we found that conditioning mice with 10% (w/v) sucrose using an oral self-administration procedure did not evoke anxietylike behavior, but elicited robust CPP, which was attenuated by ketamine treatment 30 min. prior to CPP tests. Overall, our results suggest that the ketamine-induced block of morphine CPP may not be attributed solely to alleviating negative affective states, but potentially through impaired memory of morphine-context associations.

Effect of Age in Methylphenidate-Induced Taste Avoidance and Related BDNF/Trkb in the Insular Cortex

2014 ◽  
Author(s):  
Bradley Wetzell ◽  
Mirabella M. Muller ◽  
Jennifer L. Cobuzzi ◽  
Zachary E. Hurwitz ◽  
Kathleen Decicco-Skinner ◽  
...  
Keyword(s):  
Insular Cortex ◽  
Taste Avoidance ◽  
Effect Of Age

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

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.

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.

Calcium antagonists antagonize cocaine-induced place-preference and self-administration in rats

1992 ◽  
Vol 26 ◽  
pp. 78 ◽  
Author(s):  
M.C. Martellotta ◽  
A. Kuzmin ◽  
P. Muglia ◽  
G.L. Gessa ◽  
W. Fratta
Keyword(s):  
Calcium Antagonists ◽  
Place Preference ◽  
Self Administration

Inpatient Opioid Use Disorder Treatment by Generalists is Associated With Linkage to Opioid Treatment Programs After Discharge

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Hannah R. Tierney ◽  
Christopher L. Rowe ◽  
Diana A. Coffa ◽  
Shashi Sarnaik ◽  
Phillip O. Coffin ◽  
...  
Keyword(s):  
Opioid Use Disorder ◽  
Treatment Programs ◽  
Opioid Use ◽  
Opioid Treatment ◽  
Disorder Treatment

scholarly journals Methadone Distribution Trends from 2017-2019 in the United States

2020 ◽  
Author(s):  
John A. Furst ◽  
Nicholas J. Mynarski ◽  
Kenneth L. McCall ◽  
Brian J. Piper
Keyword(s):  
United States ◽  
Rhode Island ◽  
Distribution Patterns ◽  
The United States ◽  
Opioid Use Disorder ◽  
Primary Objective ◽  
Treatment Programs ◽  
Opioid Use ◽  
Drug Enforcement ◽  
The Us

AbstractObjectiveMethadone is an evidence based treatment for opioid use disorder and is also employed for acute pain. The primary objective of this study was to explore methadone distribution patterns between the years 2017 and 2019 across the United States (US). This study builds upon previous literature that has analyzed prior years of US distribution patterns, and further outlines regional and state specific methadone trends.MethodsThe Drug Enforcement Administration’s Automated Reports and Consolidated Ordering System (ARCOS) was used to acquire the number of narcotic treatment programs (NTPs) per state and methadone distribution weight in grams. Methadone distribution by weight, corrected for state populations, and number of NTPs were compared from 2017 to 2019 between states, within regions, and nationally.ResultsBetween 2017 and 2019, the national distribution of methadone increased 12.30% for NTPs but decreased 34.57% for pain, for a total increase of 2.66%. While all states saw a decrease in distribution for pain, when compared regionally, the Northeast showed a significantly smaller decrease than all other regions. Additionally, the majority of states experienced an increase in distribution for NTPs and most states demonstrated a relatively stable or increasing number of NTPs, with an 11.49% increase in NTPs nationally. The number of NTPs per 100K in 2019 ranged from 2.08 in Rhode Island to 0.00 in Wyoming.ConclusionAlthough methadone distribution for OUD was increasing in the US, there were pronounced regional disparities.

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