scholarly journals Impact of Morphine Dependence and Withdrawal on the Reinforcing Effectiveness of Fentanyl, Cocaine, and Methamphetamine in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Robert W. Seaman Jr ◽  
Gregory T. Collins
Keyword(s):  
Opioid Dependence ◽  
Progressive Ratio ◽  
Morphine Dependence ◽  
Sprague Dawley ◽  
Self Administration ◽  
Stimulant Use ◽  
Concurrent Use ◽  
Reinforcing Effects ◽  
The Individual ◽  
The Impact

Recent estimates suggest increased popularity of the concurrent use of opioids and stimulants, with over 50% of treatment-seeking opioid users reporting regular stimulant use. The goal of the current study was to determine how opioid dependence and withdrawal affect the reinforcing effects of fentanyl, cocaine, and methamphetamine. Male Sprague-Dawley rats were allowed to self-administer fentanyl under a progressive ratio (PR) schedule of reinforcement. Baseline evaluations of reinforcing effectiveness of fentanyl, cocaine, and methamphetamine were determined. Opioid dependence was then established by administering escalating doses of morphine (10–40 mg/kg) twice-daily for four days and subsequently maintained by once-daily injections of 40 mg/kg morphine. To evaluate the impact of opioid dependence and withdrawal on the self-administration of fentanyl, cocaine, and methamphetamine, sessions occurred either 12 or 20 h after the morphine, respectively. During opioid withdrawal, the fentanyl dose-response curve was shifted rightward with an increase in maximal effectiveness, whereas it was shifted rightward with a reduction in maximal effectiveness when evaluated in rats currently dependent on opioids, relative to baseline. The reinforcing effects of cocaine and methamphetamine were unchanged by either condition. The current studies provide direct evidence that the reinforcing effects of fentanyl are increased in opioid-withdrawn rats and reduced in opioid-dependent rats, relative to rats that are not physically dependent on opioids. These findings suggest that motivations to use opioids are dependent on the state of the individual whereas stimulants retain their reinforcing effects regardless of whether the individual is in an opioid-dependent or withdrawn state.

scholarly journals 7,8-Dihydroxyflavone Enhances Cue-Conditioned Alcohol Reinstatement in Rats

2020 ◽  
Vol 10 (5) ◽  
pp. 270 ◽  
Author(s):  
Samuel J. Hogarth ◽  
Elvan Djouma ◽  
Maarten van den Buuse
Keyword(s):  
Body Weight ◽  
Progressive Ratio ◽  
Ethanol Exposure ◽  
Ethanol Solution ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Self Administration ◽  
Bdnf Expression ◽  
Sprague Dawley Rats

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.

scholarly journals Effect of amisulpride, olanzapine, quetiapine, and aripiprazole single administration on c-Fos expression in vasopressinergic and oxytocinergic neurons of the rat hypothalamic supraoptic nucleus

2020 ◽  
Vol 54 (2) ◽  
pp. 77-84
Author(s):  
Alexander Kiss ◽  
Jana Osacka
Keyword(s):  
Supraoptic Nucleus ◽  
Atypical Antipsychotics ◽  
Brain Activity ◽  
Sprague Dawley ◽  
Lower Effect ◽  
Fos Expression ◽  
The Individual ◽  
Oxytocinergic Neurons ◽  
The Impact ◽  
Hypothalamic Supraoptic Nucleus

AbstractObjective. The goal of this study was to reveal the impact of four types of atypical antipsychotics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI), with different receptor-affinity profile and dissociation constant, on the activity of hypothalamic supraoptic nucleus (SON) vasopressinergic and oxytocinergic neurons.Methods. Male Sprague Dawley rats received a single injection of vehicle (VEH) (0.1 ml/100g), AMI (20 mg/kg), OLA (5 mg/kg), QUE (15 mg/kg/) or ARI (10 mg/kg). Ninety min after treatment, the animals were fixed by transcardial perfusion, the brains removed, and cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black end product. Afterwards, the sections were exposed to vasopressin (AVP) and oxytocin (OXY) antibodies and the reaction product visualized by biotin-labeled fluorescent Alexa Fluor 568 dye. The data were evaluated from c-Fos and AVP or OXY merged sections.Results. The present study shows that all four antipsychotics applied induced c-Fos expression in the SON. With respect to the stimulation efficacy of the individual antipsychotics, estimated based on the quantity of c-Fos-labeled AVP and OXY neurons, could be a preferential action assigned to QUE over moderate effect of ARI and lower effect to OLA and reduced effect of AMI (VEH < AMI < OLA < ARI < QUE).Conclusion. The present data for the first time provide an insight into the quantitative pattern of brain activity within the clusters of SON AVP and OXY cells in response to different atypical antipsychotics single treatment.

Maternal Deprivation in Rat: Model of Vulnerability to Opiate Addiciton

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
V. Dauge
Keyword(s):  
Neuronal Development ◽  
Maternal Deprivation ◽  
Opiate Dependence ◽  
Male Rats ◽  
Morphine Dependence ◽  
Self Administration ◽  
Beneficial Effects ◽  
Individual Vulnerability ◽  
Mental Pathology ◽  
The Impact

Aims:The concept of individual vulnerability applied to mental pathology involves genetic background and/or environmental context. We studied the impact of environmental factors such as maternal deprivation on the appearance of a vulnerability to addiction. Maternal deprivation represents an early stress, a lack of nursing occurring during a period of intense neuronal development and then could lead to long term brain functioning abnormalities. It has been recently shown that > 900 genes are stably regulated by maternal care in rat.Methods:Pups were separated from their mother and littermate the day after birth 3h/day for 14 days. Place preference and oral auto-administration tests were performed at the adulthood. Opioidergic and dopaminergic systems were studied.Results:We showed that maternal deprivation leads in adult male rats to a hypersensitivity to the rewarding and reinforcing effects of morphine correlated with a basal hypoactivity of the striatal enkephalinergic system. Maternal deprivation did not change oral self-administration behavior of cocaine and alcohol. Adolescent chronic tetrahydrocannabinol exposure suppressed morphine dependence in adult deprived rats.Conclusion:Maternal deprivation represents a highly valuable model to study environmentally triggered inter-individual vulnerability to opiate addiction. The suppression of morphine dependence in adult deprived rats after adolescent chronic tetrahydrocannabinol exposure raise the question of the beneficial effects of cannabis in opiate dependence vulnerability context.

scholarly journals Contribution of Harman and Norharman to the Reinforcing Efficacy of Aqueous Tobacco Smoke Extract Self-Administered by Rats

2021 ◽  
Author(s):  
◽  
Alex John Crowther
Keyword(s):  
Tobacco Smoke ◽  
Fixed Ratio ◽  
Progressive Ratio ◽  
Sprague Dawley ◽  
Self Administration ◽  
Reinforcing Efficacy ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Reinforcing Agent

<p>Background: Animal models of drug abuse treat nicotine as the primary reinforcing agent that promotes tobacco addiction. However, rodents demonstrate poor self-administration of nicotine despite evidence of tobacco's high abuse potential in humans. This discrepancy has been attributed to other constituents of tobacco smoke that facilitate the development of nicotine dependence. Objectives: This study aimed to determine whether rats would self-administer intravenous an aqueous tobacco smoke extract (TPM) to find evidence if it was more reinforcing than nicotine alone. The study also evaluated the role of tobacco smoke constituent’s harman and norharman in any differences observed. Methods: Firstly, male Sprague-Dawley rats (n=29) were assigned to treatment groups: nicotine (30.0μg/kg/infusion), TPM (containing 30.0μg/kg/infusion nicotine) or saline vehicle. Ability for each treatment to support intravenous self-administration was assessed using spontaneous acquisition of responding on gradually increasing fixed ratio schedules (FR1, FR2, FR5). Subsequent progressive ratio (PR) testing was employed to determine reinforcing efficacy of each treatment. Then a second group of rats (N = 56) were assigned to treatment groups: nicotine alone (30.0 or 75.0μg/kg/infusion) or nicotine combined with norharman (0, 0.4, 2.5 or 6.25μg/kg/infusion) and harman (0.0, 1.6 or 10.0μg/kg, IP), and tested using a similar protocol. Results: Animals readily acquired self-administration responding for TPM and produced higher PR breakpoints (BP) than rats treated with nicotine alone or vehicle. Rats trained to respond for a larger dose of nicotine demonstrated significantly greater response rates than those receiving the lower dose of nicotine. Finally, the addition of harman and norharman to nicotine significantly reduced BP at the lower unit dose of nicotine tested. Conclusions: These findings support the hypothesis that TPM is more reinforcing than nicotine alone. However, the increased reinforcing efficacy of TPM cannot be attributed to the actions of harman and norharman. The potential role of serotonin inhibition in tobacco reward processes is discussed.</p>

scholarly journals Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

2019 ◽  
Author(s):  
Timothy G. Freels ◽  
Lydia N. Baxter-Potter ◽  
Janelle M. Lugo ◽  
Nicholas C. Glodosky ◽  
Hayden R. Wright ◽  
...  
Keyword(s):  
Fixed Ratio ◽  
Progressive Ratio ◽  
Sprague Dawley ◽  
Self Administration ◽  
Daily Food ◽  
Sprague Dawley Rats ◽  
Seeking Behavior ◽  
Break Points ◽  
Bona Fide ◽  
Novel Method

ABSTRACTRecent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug employed and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized Δ9-tetrahydrocannabinol-rich (CANTHC) or cannabidiol-rich (CANCBD) complete cannabis extracts. Male Sprague Dawley rats were trained to nosepoke for discrete puffs of CANTHC, CANCBD, or vehicle (VEH) in daily one-hour sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CANTHC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared to CANCBD or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CANTHC administration decreased hippocampal CB1 receptor binding. Removal of CANTHC reinforcement (but not CANCBD) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors.

scholarly journals The Impact of Misuse and Diversion of Opioid Substitution Treatment Medicines: Evidence Review and Expert Consensus

2015 ◽  
Vol 22 (2) ◽  
pp. 99-106 ◽  
Author(s):  
Jens Reimer ◽  
Nat Wright ◽  
Lorenzo Somaini ◽  
Carlos Roncero ◽  
Icro Maremmani ◽  
...  
Keyword(s):  
Criminal Behavior ◽  
Opioid Dependence ◽  
Direct Impact ◽  
Substitution Treatment ◽  
Negative Effects ◽  
Opioid Substitution Treatment ◽  
Controlled Drugs ◽  
The Individual ◽  
The Impact ◽  
Opioid Substitution

Background/Aims: Opioid substitution treatment (OST) improves outcomes in opioid dependence. However, controlled drugs used in treatment may be misused or diverted, resulting in negative treatment outcomes. This review defines a framework to assess the impact of misuse and diversion. Methods: A systematic review of published studies of misuse and diversion of OST medicines was completed; this evidence was paired with expert real-world experience to better understand the impact of misuse and diversion on the individual and on society. Results: Direct impact to the individual includes failure to progress in recovery and negative effects on health (overdose, health risks associated with injecting behaviour). Diversion of OST has impacts on a community that is beyond the intended OST recipient. The direct impact includes risk to others (unsupervised use; unintended exposure of children to diverted medication) and drug-related criminal behavior. The indirect impact includes the economic costs of untreated opioid dependence, crime and loss of productivity. Conclusion: While treatment for opioid dependence is essential and must be supported, it is vital to reduce misuse and diversion while ensuring the best possible care. Understanding the impact of OST misuse and diversion is key to defining strategies to address these issues.

scholarly journals Flavors Enhance Nicotine Vapor Self-administration in Male Mice

2020 ◽  
Author(s):  
Skylar Y Cooper ◽  
Austin T Akers ◽  
Brandon J Henderson
Keyword(s):  
Mouse Model ◽  
Electronic Cigarettes ◽  
Fixed Ratio ◽  
Progressive Ratio ◽  
Delivery Systems ◽  
Male Mice ◽  
Self Administration ◽  
Electronic Nicotine Delivery Systems ◽  
Nicotine Delivery ◽  
The Impact

Abstract Introduction Although the use of combustible cigarettes has decreased in many urban regions of America, the use of electronic nicotine delivery systems (ENDS) has dramatically increased. ENDS, or electronic cigarettes (e-cigarettes), differ from combustible cigarettes given that there are no restrictions on flavorant additives in e-liquids. With 95% of ENDS users vaping flavored e-liquids, it is critical to understand how flavors alter vaping-related behaviors. We have previously shown that menthol and green apple flavors enhance nicotine reward-related behavior in a mouse model and in the present study have investigated how menthol and green apple flavors alter e-Vape self-administration behavior in male mice. Methods Adult C57/BL6J male mice were used in vapor-inhalation self-administration assays. Mice were assigned vaping e-liquids (6 mg/mL nicotine with or without menthol or green apple flavor) to escalate on a fixed-ratio 1 (FR1) schedule in daily 3-hour sessions to examine initiation-related behaviors. Following escalation, mice were transitioned to a FR3 and progressive ratio schedules in 3-hour sessions to examine reinforcement-related behaviors. Results Here we observed that male mice exhibited increased rates of self-administration escalation on a FR1 schedule when assigned to flavored e-liquids. Upon transition to FR3, mice continued to exhibit enhanced levels of reinforcement with flavored e-liquids. We also observed that mice self-administer zero-nicotine green apple flavored e-liquids. Conclusions These data provide additional evidence that ENDS flavors enhance vaping-related initiation and reinforcement-related behavior and promote the need to continue investigating the role ENDS flavors play in vaping-related behaviors. Implications There has been much discussion recently regarding the impact of flavors on vaping-related behavior. Our study here shows that flavors significantly enhance the acquisition and reinforcement of vaping-related behavior. This suggests that flavors in electronic nicotine delivery systems significantly increase the risk of addiction-related behaviors among users of vaping products.

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