Browsing by Subject "Self Administration"
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Item Open Access Acute and chronic interactive treatments of serotonin 5HT2C and dopamine D1 receptor systems for decreasing nicotine self-administration in female rats.(Pharmacology, biochemistry, and behavior, 2019-11) Willette, Blair KA; Nangia, Anica; Howard, Sarah; DiPalma, Devon; McMillan, Collin; Tharwani, Sonum; Evans, Janequia; Wells, Corinne; Slade, Susan; Hall, Brandon J; Rezvani, Amir H; Levin, Edward DA variety of neural systems are involved in the brain bases of tobacco addiction. Animal models of nicotine addiction have helped identify a variety of interacting neural systems involved in the pathophysiology of tobacco addiction. We and others have found that drug treatments affecting many of those neurotransmitter systems significantly decrease nicotine self-administration. These treatments include dopamine D1 receptor antagonist, histamine H1 antagonist, serotonin 5HT2C agonist, glutamate NMDA antagonist, nicotinic cholinergic α4β2 partial agonist and nicotinic cholinergic α3β4 antagonist acting drugs. It may be the case that combining treatments that affect different neural systems underlying addiction may be more efficacious than single drug treatment. In the current study, we tested the interactions of the D1 antagonist SCH-23390 and the serotonin 5HT2c agonist lorcaserin, both of which we have previously shown to significantly reduce nicotine self-administration. In the acute interactions study, both SCH-23390 and lorcaserin significantly reduced nicotine self-administration when given alone and had additive effects when given in combination. In the chronic study, each drug alone caused a significant decrease in nicotine self-administration. No additive effect was seen in combination because SCH-23390 given alone chronically was already highly effective. Chronic administration of the combination was not seen to significantly prolong reduced nicotine self-administration into the post-treatment period. This research shows that unlike lorcaserin and SCH-23390 interactions when given acutely, when given chronically in combination they do not potentiate or prolong each other's effects in reducing nicotine self-administration.Item Open Access Amitifadine, a triple reuptake inhibitor, reduces self-administration of the opiate remifentanil in rats.(Psychopharmacology, 2020-06) Levin, Edward D; Wells, Corinne; Hawkey, Andrew; Holloway, Zade; Blair, Graham; Vierling, Alexander; Ko, Ashley; Pace, Caroline; Modarres, John; McKinney, Anthony; Rezvani, Amir H; Rose, Jed ERationale
A variety of neural systems are involved in drug addiction, and some of these systems are shared across different addictive drugs. We have found several different types of drug treatments that successfully reduce nicotine self-administration.Objectives
The current set of studies is the first in a series to determine if drug treatments that have been found to significantly reduce nicotine self-administration would reduce opiate self-administration.Methods
Amitifadine, a triple reuptake inhibitor of dopamine, norepinephrine, and serotonin, was assessed in female Sprague-Dawley rats to determine whether it significantly reduces remifentanil self-administration with either acute or chronic treatment.Results
Acutely, amitifadine doses of 5, 10, and 20 mg/kg each significantly reduced remifentanil self-administration. In a chronic study, repeated treatment with 10 mg/kg of amitifadine continued to reduce remifentanil self-administration, even after the cessation of treatment. However, amitifadine was not found to attenuate the rise in remifentanil self-administration with continued access. This study and our earlier one showed that the 10 mg/kg amitifadine dose did not significantly affect food motivated responding. Amitifadine did not attenuate remifentanil-induced antinociception as measured on the hot plate test but extended and maintained antinociceptive effects.Conclusions
These studies show the promise of amitifadine as a treatment for countering opiate self-administration for adjunctive use with opioids for analgesia. Further studies are needed to determine the possible efficacy of amitifadine for combating opiate addiction or preventing it in humans during adjunctive use with opioids for chronic pain.Item Open Access Chronic infusions of mecamylamine into the medial habenula: Effects on nicotine self-administration in rats.(Behavioural brain research, 2022-01) Levin, Edward D; Wells, Corinne; Slade, Susan; Johnson, Joshua; Petro, Ann; Rezvani, Amir H; Rose, Jed EThe habenula is an epithalamic structure through which descending connections go from the telencephalon to the brainstem, putting it in a key location to provide feedback control over the ascending projections from the brainstem to the telencephalon. The medial habenula has a high concentration of nicotinic receptors. We assessed the role of medial habenular nicotinic receptors for nicotine self-administration (SA) in female young adult Sprague-Dawley rats. The rats had bilateral chronic infusion cannulae placed into the medial habenula nucleus. Each cannula was connected to a slow delivery osmotic minipump to chronically infuse mecamylamine (100 µg/side/day) or vehicle for four consecutive weeks. The rats were tested for nicotine SA for the first two weeks of mecamylamine infusion. Then, they had one week of enforced abstinence, during which they had no access to the nicotine SA. Finally, they had one week of resumed nicotine SA access. There was a significantly differential mecamylamine effects in animals with lower and higher pretreatment baseline nicotine SA. Rats with lower baseline nicotine SA levels showed a nearly significant mecamylamine-induced reduction in SA while those with higher baseline levels of SA showed a significant mecamylamine-induced increase in nicotine SA. This study determined that medial habenular nicotinic receptors are important for nicotine reinforcement. Baseline level of performance makes a crucial difference for the involvement of habenular mechanisms in nicotine reinforcement with nicotinic activation being important for maintaining nicotine self-administration for those with lower levels of baseline self-administration and the opposite effect with subjects with higher levels of baseline self-administration.Item Open Access Chronic memantine decreases nicotine self-administration in rats.(European journal of pharmacology, 2019-10) Levin, Edward D; Wells, Corinne; Yao, Leah; Guo, Wendi; Nangia, Anica; Howard, Sarah; Pippen, Erica; Hawkey, Andrew B; Rose, Jed E; Rezvani, Amir HNeurobehavioral bases of tobacco addiction and nicotine reinforcement are complex, involving more than only nicotinic cholinergic or dopaminergic systems. Memantine is an NMDA glutamate antagonist used to improve cognitive function in people with Alzheimer's disease. Glutamate may be an important component of the reinforcing effects of nicotine, so memantine was evaluated as a potential smoking cessation aid. Two studies were conducted with adult female rats, one testing acute effects of memantine over a range of doses for changing nicotine self-administration and the other testing the chronic effects of memantine to reduce nicotine self-administration. Acute memantine injections slightly, but significantly, increased nicotine self-administration in a dose-related manner. In contrast, chronic memantine treatment significantly reduced nicotine self-administration. During the first day of memantine administration in the chronic study, nicotine self-administration was significantly elevated replicating the acute study. Starting in the second week of treatment there was a significant reduction of nicotine self-administration relative to controls. This was seen because memantine treatment prevented the increase in nicotine self-administration shown by controls. There even continued to be a memantine-induced lowered nicotine self-administration during the week after the cessation of memantine treatment. Memantine or other drugs affecting NMDA glutamate receptors may be useful aids to smoking cessation. Full efficacy for reducing nicotine self-administration was seen as the NMDA drug treatment is given chronically. Importantly, the effect persisted even after treatment is ended, indicating the high potential for NMDA glutamate receptors to impact nicotine addiction.Item Open Access Differential behavioral functioning in the offspring of rats with high vs. low self-administration of the opioid agonist remifentanil.(European journal of pharmacology, 2021-10) Rezvani, Amir H; Wells, Corinne; Hawkey, Andrew; Blair, Graham; Koburov, Reese; Ko, Ashley; Schwartz, Andrea; Kim, Veronica J; Levin, Edward DOpioid use disorder (OUD) has a variety of adverse effects on both the users and their offspring. In the current study, a random group of Sprague-Dawley rats (25 females and 15 males) were tested for intravenous self-administration of the opioid agonist remifentanil to determine the range of acquisition for opioid. One-month after the end of self-administration of remifentanil, rats with the highest intake were mated together and rats with lowest intake were mated together. Then, the offspring of the two groups were tested for anxiety-like behavior, locomotor activity, nociception and intravenous remifentanil self-administration. The parents showed a range of remifentanil self-administration, especially in the female rats. The offspring of the parents with low and high remifentanil self-administration showed significant differences in specific behavioral functions. On the hotplate test of nociception, the female offspring parents with high remifentanil self-administration had significantly longer hotplate latencies, indicating reduced nociception, than the female offspring of parents with low remifentanil-self-administration, whereas there was no difference in the male offspring of low and high responding parents. In the elevated plus maze test of anxiety-like behavior, the offspring of the parents with high remifentanil intake showed more anxiety-like behavior than the offspring of the parents with low remifentanil intake regardless of sex. Locomotor activity was not significantly different. Interestingly, no significant differences in remifentanil self-administration in the offspring of parents with low and high remifentanil self-administration were detected. Overall, our data suggest a considerable range in remifentanil self-administration in rats and the offspring of rats with high opioid self-administration exhibit different behaviors vs offspring of rats with low opioid self-administration.Item Open Access Medication non-adherence after myocardial infarction: an exploration of modifying factors.(Journal of general internal medicine, 2015-01) Crowley, Matthew J; Zullig, Leah L; Shah, Bimal R; Shaw, Ryan J; Lindquist, Jennifer H; Peterson, Eric D; Bosworth, Hayden BBackground
Medication non-adherence is a major impediment to the management of cardiovascular disease risk factors. A better understanding of the modifying factors underlying medication non-adherence among individuals with known cardiovascular disease may inform approaches for addressing non-adherence.Objective
The purpose of this study was to identify demographic and patient characteristics, medical comorbidities, psychosocial factors, and health belief-related factors associated with medication non-adherence among patients with known cardiovascular disease.Design
We performed secondary analysis of baseline data from a randomized trial.Patients
The study included 405 patients with a diagnosis of hypertension and history of acute myocardial infarction that was diagnosed within a three-year period prior to enrollment.Main measures
Baseline demographics and patient characteristics, medical comorbidities, psychosocial factors, health belief-related factors, and patient-reported medication non-adherence were analyzed.Key results
Of 405 patients, 173 (42.7 %) reported medication non-adherence. Factors associated with non-adherence in bivariate analysis included younger age, non-white race, having less than 12 years of education, smoking, financial insecurity, identifying as nervous or tense, higher life chaos score, greater worry about having a myocardial infarction, and greater worry about having a stroke. Using multivariable modeling, we determined that age (OR 0.97 per additional year, 95 % CI, 0.95-0.99), life chaos (OR 1.06 per additional point, 95 % CI, 1.00-1.11), and worry about stroke (OR 1.12 per additional point, 95 % CI, 1.01-1.25) remained significantly associated with self-reported medication non-adherence.Conclusions
We found that worry about having a stroke, higher life chaos, and younger age were all significantly associated with self-reported medication non-adherence in patients with cardiovascular disease and a history of myocardial infarction. Further research exploring these factors as targets for intervention is needed, as is additional research examining modifiable causes of medication non-adherence among patients with cardiovascular disease.Item Open Access Non-prescribed use of pain relievers among adolescents in the United States.(Drug and alcohol dependence, 2008-04) Wu, Li-Tzy; Pilowsky, Daniel J; Patkar, Ashwin AWe examined gender-specific prevalences, patterns, and correlates of non-prescribed use of pain relievers - mainly opioids - in a representative sample of American adolescents (N=18,678).Data were drawn from the public use data file of the 2005 U.S. National Survey on Drug Use and Health, a survey of non-institutionalized American household residents. The patterns of non-prescribed use of prescription pain relievers were examined, and logistic regression procedures were conducted to identify correlates of non-prescribed use.Approximately one in 10 adolescents aged 12-17 years reported non-prescribed use of pain relievers in their lifetime (9.3% in males and 10.3% in females). The mean age of first non-prescribed use was 13.3 years, which was similar to the mean age of first use of alcohol and marijuana but older than the age of first inhalant use. Among all non-prescribed users, 52% reported having used hydrocodone products (Vicodin, Lortab, Lorcet, and Lorcet Plus, and hydrocodone), 50% had used propoxyphene (Darvocet or Darvon) or codeine (Tylenol with codeine), and 24% had used oxycodone products (OxyContin, Percocet, Percodan, and Tylox). Approximately one quarter (26%) of all non-prescribed users had never used other non-prescribed or illicit drugs. There were gender variations in correlates of non-prescribed use.Use of non-prescribed pain relievers occurs early in adolescence. Research is needed to understand whether early use of non-prescribed pain relievers is related to later drug use.Item Open Access Potential economic viability of two proposed rifapentine-based regimens for treatment of latent tuberculosis infection.(PLoS One, 2011) Holland, David P; Sanders, Gillian D; Hamilton, Carol D; Stout, Jason ERATIONALE: Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. OBJECTIVES: To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). METHODS: We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of "no treatment" used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. RESULTS: Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. CONCLUSIONS: Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced, study designers should consider relaxing non-inferiority boundaries.Item Open Access Self-administration by female rats of low doses of nicotine alone vs. nicotine in tobacco smoke extract.(Drug and alcohol dependence, 2021-11) Levin, Edward D; Wells, Corinne; Pace, Caroline; Abass, Grant; Hawkey, Andrew; Holloway, Zade; Rezvani, Amir H; Rose, Jed EBackground
Nicotine has reinforcing effects, but there are thousands of other compounds in tobacco, some of which might interact with nicotine reinforcement.Aims
This rat study was conducted to determine if nicotine self-administration is altered by co-administration of the complex mixture of compounds in tobacco smoke extract (TSE).Methods
Female Sprague-Dawley rats were tested for self-administration of low doses of nicotine (3 or 10 µg/kg/infusion) at three different rates of reinforcement (FR1, FR3 and FR5) over three weeks either alone or together with the complex mixture of tobacco smoke extract (TSE).Results
Rats self-administering 3 µg/kg/infusion of nicotine alone showed a rapid initiation on an FR1 schedule, but declined with FR5. Rats self-administering nicotine in TSE acquired self-administration more slowly, but increased responding over the course of the study. With 10 µg/kg/infusion rats self-administered significantly more nicotine alone than rats self-administering the same nicotine dose in TSE. Rats self-administering nicotine alone took significantly more infusions with the 10 than the 3 µg/kg/infusion dose, whereas rats self-administering nicotine in TSE did not. Nicotine in TSE led to a significantly greater locomotor hyperactivity at a dose of 0.1 mg/kg compared to rats that received nicotine alone. Rats self-administering nicotine alone had significantly more responding on the active vs. inactive lever, but rats self-administering the same nicotine doses in TSE did not.Conclusions
Self-administration of nicotine in a purer form appears to be more clearly discriminated and dose-related than nicotine self-administered in the complex mixture of TSE.Item Open Access Self-monitoring and self-titration of antihypertensive medication reduces systolic blood pressure compared with usual care.(Evidence-based nursing, 2015-07) Bosworth, Hayden B; Crowley, Matthew JItem Open Access α4β2 Nicotinic receptor desensitizing compounds can decrease self-administration of cocaine and methamphetamine in rats.(European journal of pharmacology, 2019-02) Levin, Edward D; Rezvani, Amir H; Wells, Corinne; Slade, Susan; Yenugonda, Venkata M; Liu, Yong; Brown, Milton L; Xiao, Yingxian; Kellar, Kenneth JSazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a selective α4β2 nicotinic receptor desensitizing agent and partial agonist. Sazetidine-A has been shown in our previous studies to significantly reduce nicotine and alcohol self-administration in rats. The question arises whether sazetidine-A would reduce self-administration of other addictive drugs as well. Nicotinic receptors on the dopaminergic neurons in the ventral tegmental area play an important role in controlling the activity of these neurons and release of dopamine in the nucleus accumbens, which is critical mechanism for reinforcing value of drugs of abuse. Previously, we showed that the nonspecific nicotinic antagonist mecamylamine significantly reduces cocaine self-administration in rats. In this study, we acutely administered systemically sazetidine-A and two other selective α4β2 nicotinic receptor-desensitizing agents, VMY-2-95 and YL-2-203, to young adult female Sprague-Dawley rats and determined their effects on IV self-administration of cocaine and methamphetamine. Cocaine self-administration was significantly reduced by 0.3 mg/kg of sazetidine-A. In another set of rats, sazetidine-A (3 mg/kg) significantly reduced methamphetamine self-administration. VMY-2-95 significantly reduced both cocaine and methamphetamine self-administration with threshold effective doses of 3 and 0.3 mg/kg, respectively. In contrast, YL-2-203 did not significantly reduce cocaine self-administration at the same dose range and actually significantly increased cocaine self-administration at the 1 mg/kg dose. YL-2-203 (3 mg/kg) did significantly decrease methamphetamine self-administration. Sazetidine-A and VMY-2-95 are promising candidates to develop as new treatments to help addicts successfully overcome a variety of addictions including tobacco, alcohol as well as the stimulant drugs cocaine and methamphetamine.