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1.
Psychon Bull Rev ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769272

ABSTRACT

Nicotine produces robust stimulus effects that can be conditioned to form associations with reinforcing nondrug stimuli. We examine how established associations to the nicotine stimulus may be weakened via the overexpectation effect. In two experiments, we separately conditioned sucrose associations to the interoceptive nicotine stimulus (0.4 mg/kg, SC) and to a "noisy" exteroceptive contextual stimulus (oscillating houselight and white noise) via the discriminated goal-tracking task. Thereafter, we presented additional sucrose pairings with the nicotine and noisy stimuli, now in compound. Testing of the conditioned goal-tracking evoked by the nicotine and noisy stimuli in isolation-before versus after compound conditioning (Experiment 1) or between treatment and control groups (Experiment 2)-demonstrated an attenuation of conditioned responding via the overexpectation effect. We suggest that applications of the overexpectation effect may provide some promise for treatments seeking to attenuate drug-evoked conditioned responses in situations where extinction-based interventions are not suitable.

2.
MethodsX ; 12: 102675, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38585181

ABSTRACT

Intravenous self-administration in rats is used widely to study the reinforcing effects of drugs and serves as the gold standard for assessing their use and misuse potential. One challenge that researchers often encounter when scaling up experiments is balancing the cost, time investment to construct, and robustness of each implanted catheter. These catheters include multiple components such as surgical meshing and a variety of entry ports designed to facilitate the connection of the rat to a catheter port tethering system. Other considerations include maintaining the catheters free of blockage during the extent of the drug self-administration experiment. These large-scale studies provide ample opportunity for the catheter system to fail. The failure and replacement of commercially purchased catheters leads to ballooning expenses, and the failure of in-lab manufactured catheters requires the manufacture of reserves, also increasing costs, as these handmade products are inherently more variable. We have developed a catheter system that combines a commercially available implantable back-mounted entry connector system with inexpensive medical items such as surgical mesh, sutures, and an air-tight back flow prevention system to bolster the overall success of self-administration experiments.•Method to bolster commercially available jugular catheter components for long-lasting self-administration experiments.•Reduces the overall cost per unit of self-administration experiments.•Easily assembled by laboratory students and staff.

3.
Int J Drug Policy ; 127: 104400, 2024 May.
Article in English | MEDLINE | ID: mdl-38554564

ABSTRACT

BACKGROUND: Following the passage of the 2018 Farm Bill, derived psychoactive cannabis products containing delta 8 tetrahydrocannabinol (THC) have become increasingly popular across the US, particularly in states that lack medical or recreational cannabis programs. Despite this, little is known about patterns of delta 8 THC use. METHODS: A sample of Nebraska residents (a state without legal medical or recreational cannabis) were surveyed to gather data on substance use, including delta 8 THC and cannabis, across the state. Then, logistic regressions were used to calculate relative odds ratios to understand the factors that increased the likelihood at which Nebraska residents use delta 8 THC or cannabis products. RESULTS: Analysis revealed that younger adults have higher odds of delta 8 THC use but not cannabis and that non-white participants had higher odds of delta 8 use than white non-Hispanic groups but there was no difference for cannabis use. Political affiliation, sexual orientation, access, and knowledge of friends who used cannabis were also associated with cannabis use but not delta 8 THC use. Past substance use and personal opinion regarding cannabis use increased likelihood for both delta 8 THC and cannabis use. CONCLUSION: These results illuminate several factors which affect cannabis and delta 8 THC use while providing insight on the people that are most likely to be impacted by the potential consequences of substance use, especially when considering the inconsistent laws governing cannabis and delta 8 THC use across the US.


Subject(s)
Dronabinol , Humans , Nebraska , Adult , Female , Male , Young Adult , Adolescent , Middle Aged , Cannabis/chemistry , Marijuana Smoking/epidemiology , Marijuana Use/epidemiology , Surveys and Questionnaires , Legislation, Drug , Age Factors , Aged
4.
Harm Reduct J ; 21(1): 37, 2024 Feb 10.
Article in English | MEDLINE | ID: mdl-38336722

ABSTRACT

BACKGROUND: The rising prevalence of fast-acting opioids in the USA suggests the increased need for non-professional first responder administration of naloxone. Effective administration of naloxone during an overdose requires that bystanders are familiar with, have access to, and know how to use naloxone. METHODS: Drawing on a statewide, address-based sample of Nebraskan adults, we used logistic regression to predict the likelihood of respondents' familiarity with, access to, and competency to administer naloxone. Our independent variables included measures indicating proximity to drug use, perceived community stigma toward people who use drugs, and demographic data. RESULTS: There were significant gaps in naloxone knowledge in Nebraska. Although 74.8% of respondents were familiar with naloxone, only 18.2% knew how to access it and 18.0% knew how to use it. Being close to an overdose experience, lifetime illicit opioid use, being close to a person who uses opioids, and having access to illicit opioids were not significantly associated with naloxone familiarity, access, or competency among respondents in Nebraska's two largest cities, Omaha and Lincoln. Outside of these cities, being close to a past overdose experience and access to illicit opioids was associated with higher odds of naloxone access and competency, but lifetime opioid use and being close to a person who uses opioids were not. Finally, among those familiar with naloxone, a higher perception of community stigma toward people who use opioids generally was associated with lower odds of naloxone access and competency. Higher perception of community stigma toward people who use heroin, methamphetamines, and cocaine, however, was associated with higher odds of naloxone access. CONCLUSIONS: Our findings highlight the continued need for education on naloxone with a specific focus on access and competency to further reduce opioid-related overdose deaths. Specific focus should be placed on promoting naloxone knowledge among people with a higher likelihood of needing to administer naloxone to reduce otherwise avoidable deaths. Further work is needed to understand differences in the relationship between substance-specific perceived stigma and its association with naloxone access.


Subject(s)
Drug Overdose , Opiate Overdose , Opioid-Related Disorders , Adult , Humans , Naloxone/therapeutic use , Analgesics, Opioid/therapeutic use , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Heroin/therapeutic use , Drug Overdose/drug therapy , Opiate Overdose/drug therapy , Surveys and Questionnaires , Narcotic Antagonists/therapeutic use
5.
Horm Behav ; 161: 105506, 2024 May.
Article in English | MEDLINE | ID: mdl-38387104

ABSTRACT

Estradiol and progesterone potentiate and attenuate reward processes, respectively. Despite these well-characterized effects, there is minimal research on the effects of synthetic estrogens (e.g., ethinyl estradiol, or EE) and progestins (e.g., levonorgestrel, or LEVO) contained in clinically-utilized hormonal contraceptives. The present study characterized the separate effects of repeated exposure to EE or LEVO on responding maintained by a reinforcing visual stimulus. Forty ovary-intact female Sprague-Dawley rats received either sesame oil vehicle (n = 16), 0.18 µg/day EE (n = 16), or 0.6 µg/day LEVO (n = 8) subcutaneous injections 30-min before daily one-hour sessions. Rats' responding was maintained by a 30-sec visual stimulus on a Variable Ratio-3 schedule of reinforcement. The day after rats' last session, we determined rats estrous cycle phase via vaginal cytology before sacrifice and subsequently weighing each rat's uterus to further verify the contraceptive hormone manipulation. The visual stimulus functioned as a reinforcer, but neither EE nor LEVO enhanced visual stimulus maintained responding. Estrous cytology was consistent with normal cycling in vehicle rats and halting of normal cycling in EE and LEVO rats. EE increased uterine weights consistent with typical uterotrophic effects observed with estrogens, further confirming the physiological impacts of our EE and LEVO doses. In conclusion, a physiologically effective dose of neither EE nor LEVO did not alter the reinforcing efficacy of a visual stimulus reinforcer. Future research should characterize the effects of hormonal contraceptives on responding maintained by other reinforcer types to determine the generality of the present findings.


Subject(s)
Ethinyl Estradiol , Levonorgestrel , Rats, Sprague-Dawley , Animals , Female , Ethinyl Estradiol/pharmacology , Ethinyl Estradiol/administration & dosage , Levonorgestrel/pharmacology , Levonorgestrel/administration & dosage , Rats , Reinforcement, Psychology , Photic Stimulation/methods , Ovary/drug effects , Estrous Cycle/drug effects
6.
Pharmacol Biochem Behav ; 235: 173702, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38154590

ABSTRACT

Smoking is the leading cause of preventable death worldwide, with <7 % of smoking cessation attempts being met with success. Nicotine, the main addictive agent in cigarettes, enhances the reinforcing value of other environmental rewards. Under some circumstances, this reward enhancement maintains nicotine consumption. Varenicline (i.e., cessation aid Chantix™) also has reward-enhancement effects via nicotinic acetylcholine receptor agonism (nAChRs) - albeit less robust than nicotine. Cotinine is the major metabolite of nicotine. Recent studies suggest that cotinine is a positive allosteric modulator (PAM) and/or a weak agonist at nAChRs. Thus, cotinine may enhance the behavioral effects of nAChR compounds such as varenicline and/or exert some behavioral effects alone. We used 20 (10M, 10F) Sprague-Dawley rats to assess reward-enhancement within-subjects by examining responding maintained by a reinforcing visual stimulus on a Variable Ratio 2 schedule of reinforcement. To assess the reward-enhancing effects of cotinine, rats received one injection of cotinine (saline, 0.1, 0.3, 1.0, 3.0, 6.0 mg/kg) before each 1 h session. To assess cotinine and varenicline interactions, rats received an injection of cotinine (saline, 0.1, 1.0, or 6.0 mg/kg) and of varenicline (saline, 0.1, 0.3, 1.0, or 3.0 mg/kg) before the session. While we replicated prior work identifying reward-enhancement by 0.1, 0.3, and 1.0 mg/kg varenicline, cotinine alone did not produce reward-enhancement nor augment the reward-enhancing effects of varenicline. Future studies may consider examining the reward-enhancing effects of cotinine with other reinforcers or co-administered with other smoking cessation aids such as bupropion.


Subject(s)
Nicotine , Receptors, Nicotinic , Humans , Rats , Animals , Varenicline/pharmacology , Nicotine/pharmacology , Cotinine/pharmacology , Rats, Sprague-Dawley , Nicotinic Agonists/pharmacology , Receptors, Nicotinic/metabolism , Benzazepines/pharmacology , Quinoxalines/pharmacology
7.
Res Sq ; 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37961638

ABSTRACT

Background: The rising prevalence of fast-acting opioids in the United States suggests the increased need for non-first responder administration of naloxone. Effective administration of naloxone during an overdose requires that bystanders are familiar with, have access to, and know how to use naloxone. Methods: Drawing on the 2022 Nebraska Annual Social Indicators survey, we analyzed naloxone familiarity, access, and competency to administer among a statewide, address-based sample of Nebraskan adults. Results: There were significant gaps in naloxone knowledge in Nebraska. Although 75.6% of respondents were familiar with naloxone, only 18.6% knew how to access naloxone and 17.6% knew how to use naloxone. We find that more frequent religious service attendance is associated with lower odds of naloxone familiarity. Among those familiar with naloxone, a higher perception of community stigma towards opioids generally is associated with lower odds of naloxone access and competency. Higher perception of community stigma towards heroin, methamphetamines, and cocaine, however, is associated with higher odds of naloxone access. Finally, past overdose experience, lifetime illicit opioid use, being close to a person who uses opioids, and having access to illicit opioids was not significantly associated with naloxone familiarity, access, or competency among respondents in Nebraska's two largest cities, Omaha and Lincoln. Outside of these cities, past overdose experience and access to illicit opioids was associated with higher odds of naloxone access and competency, but lifetime opioid use and being close to a person who uses opioids had no effect. Conclusions: Our findings highlight the continued need for education on naloxone with a specific focus on access and competency to further reduce opioid-related overdose deaths. Education campaigns targeted at places of worship or individuals close to people who use opioids may further serve those with a lower likelihood of naloxone familiarity and promote knowledge of naloxone among those with higher odds of encountering an overdose. Further work is needed to understand differences in the relationship between substance-specific perceived stigma and its association with naloxone access.

8.
Drug Alcohol Depend ; 248: 109906, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37216808

ABSTRACT

BACKGROUND: Nicotine is commonly co-used with other psychostimulants. These high co-use rates have prompted much research on interactions between nicotine and psychostimulant drugs. These studies range from examination of illicitly used psychostimulants such as cocaine and methamphetamine to prescription psychostimulants used to treat attention deficit hyperactivity disorder (ADHD) such as methylphenidate (Ritalin™) and d-amphetamine (active ingredient of Adderall™). However, previous reviews largely focus on nicotine interactions with illicitly used psychostimulants with sparse mention of prescription psychostimulants. The currently available epidemiological and laboratory research, however, suggests high co-use between nicotine and prescription psychostimulants, and that these drugs interact to modulate use liability of either drug. The present review synthesizes epidemiological and experimental human and pre-clinical research assessing the behavioral and neuropharmacological interactions between nicotine and prescription psychostimulants that may contribute to high nicotine-prescription psychostimulant co-use. METHODS: We searched databases for literature investigating acute and chronic nicotine and prescription psychostimulant interactions. Inclusion criteria were that participants/subjects had to experience nicotine and a prescription psychostimulant compound at least once in the study, in addition to assessment of their interaction. RESULTS AND CONCLUSIONS: Nicotine clearly interacts with d-amphetamine and methylphenidate in a variety of behavioral tasks and neurochemical assays assessing co-use liability across preclinical, clinical, and epidemiological research. The currently available research suggests research gaps examining these interactions in women/female rodents, in consideration of ADHD symptoms, and how prescription psychostimulant exposure influences later nicotine-related outcomes. Nicotine has been less widely studied with alternative ADHD pharmacotherapy bupropion, but we also discuss this research.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Methylphenidate , Female , Humans , Nicotine/pharmacology , Nicotine/therapeutic use , Central Nervous System Stimulants/pharmacology , Central Nervous System Stimulants/therapeutic use , Methylphenidate/pharmacology , Methylphenidate/therapeutic use , Attention Deficit Disorder with Hyperactivity/drug therapy , Dextroamphetamine/therapeutic use , Prescriptions
9.
Behav Pharmacol ; 34(1): 12-19, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36730812

ABSTRACT

Varenicline (Chantix) is an FDA-approved smoking cessation aid that is pharmacologically similar to nicotine, the primary addictive component found within tobacco. In support of this similarity, previous drug discrimination research in rats has reported that the internal or interoceptive stimulus effects of nicotine and varenicline share stimulus elements. Those shared elements appear to be mediated, in part, by overlapping action at alpha4beta2-containing nicotinic acetylcholine receptors (nAChRs). The research supporting this conclusion, however, has only used nicotine, and not varenicline, as the training drug. Accordingly, we used the discriminated goal tracking (DGT) task in which 1 mg/kg varenicline signaled intermittent access to sucrose. On separate intermixed saline days, sucrose was not available. Rats acquired the discrimination as measured by a differential increase in dipper entries (goal tracking) evoked by varenicline. These rats then received a series of tests with several doses of varenicline, nicotine, nornicotine (a metabolite of nicotine and tobacco alkaloid), sazetidine-A (a partial alpha4beta2 agonist), PHA-543613 (an alpha7 agonist), and bupropion (a norepinephrine and dopamine reuptake inhibitor). Control of goal tracking by varenicline was dose-dependent. Nicotine and nornicotine evoked responding comparable to the varenicline training dose indicating full substitution. Sazetidine-A partially substituted for the varenicline stimulus, whereas bupropion and PHA-543613 evoked little to no varenicline-like responding. These findings indicate that varenicline can serve as the training stimulus in the DGT task. Further, stimulus control of varenicline in the DGT task is driven by its partial agonist activity at alpha4beta2-containing nAChRs. The use of this approach could lead to a better understanding of the pharmacological action of varenicline and help guide treatment geared towards tobacco cessation through a more targeted development of novel synthetically designed, subunit-specific pharmacological interventions.


Subject(s)
Motivation , Receptors, Nicotinic , Smoking Cessation Agents , Varenicline , Animals , Rats , Benzazepines/pharmacology , Bupropion , Goals , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Quinoxalines/pharmacology , Receptors, Nicotinic/metabolism , Varenicline/pharmacology , Smoking Cessation Agents/pharmacology , Motivation/drug effects
10.
Psychopharmacology (Berl) ; 240(11): 2221-2230, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36656336

ABSTRACT

RATIONALE: Translational research, especially research that bridges studies with humans and nonhuman species, is critical to advancing our understanding of human disorders such as addiction. This advancement requires reliable and rigorous models to study the underlying constructs contributing to the maladaptive behavior. OBJECTIVE: In this commentary, we address some of the challenges of conducting translational research by examining a single procedure, place conditioning. Place conditioning is commonly used with laboratory animals to study the conditioned rewarding effects of drugs, and recent studies indicate that a similar procedure can be used in humans. RESULTS: We discuss the opportunities and challenges of making the procedure comparable across species, as well as discuss the benefits of more systematically applying the procedure to humans. CONCLUSION: We argue that the capacity of humans to report verbally on their internal experiences (perceptions, affective states, likes and dislikes) add an important dimension to the understanding of the procedures used in laboratory animals.


Subject(s)
Behavior, Addictive , Translational Research, Biomedical , Animals , Humans , Emotions , Reward
12.
J Exp Anal Behav ; 117(3): 543-559, 2022 05.
Article in English | MEDLINE | ID: mdl-35192221

ABSTRACT

Nicotine produces robust stimulus effects that can be conditioned to exert stimulus control over behavior through associative learning. Additionally, nicotine has weak reinforcing effects that are inconsistent with its prevalence of use and the tenacity of nicotine dependence. The present study investigated whether conditioned associations to the nicotine drug stimulus may confer additional reinforcing strength to nicotine that thereby increase its use liability, and presents a new methodological approach to investigating the interaction between the stimulus effects and reinforcing effects of drugs. Male and female Sprague-Dawley rats were divided into groups receiving intravenous infusions of either 0.03 mg/kg nicotine or 0.9% saline that were either Paired (30 s delayed) or explicitly Unpaired (4 to 6 min delayed) with sucrose deliveries over 24 daily conditioning sessions. Thereafter, recessed nosepoke response devices were installed in the chambers and infusions of their assigned drug solutions were contingently available according to a progressive ratio schedule. Rats in the Paired Nicotine condition acquired the nosepoke response, expressed active nosepoke discrimination, and self-administered significantly more infusions than rats in any of the other groups. These results demonstrate that the interoceptive stimulus effects of nicotine can form Pavlovian associations with reinforcing events that alter its reinforcement efficacy.


Subject(s)
Nicotine , Nicotinic Agonists , Animals , Conditioning, Classical , Conditioning, Operant , Female , Male , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Rats , Rats, Sprague-Dawley , Reinforcement, Psychology
13.
Psychopharmacology (Berl) ; 239(3): 819-830, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35137248

ABSTRACT

RATIONALE: Bupropion is a non-nicotine medication for smoking cessation that has overlapping stimulus effects with nicotine as demonstrated in drug discrimination studies. Whether these shared stimulus effects will alter acquisition or maintenance of a discrimination between nicotine and bupropion is unknown. OBJECTIVE: We sought to test this possibility using the drug discriminated goal-tracking (DGT) task and whether discrimination training history affected generalization and substitution tests. METHODS: Sixty adult Sprague-Dawley rats (30M/30F) were equally split into three discrimination training groups: SAL-0.4NIC, 10BUP-0.4NIC, and 20BUP-0.4NIC. On nicotine days, all rats were administered subcutaneously 0.4 mg/kg nicotine and had intermittent access to liquid sucrose. On intermixed non-reinforced days, rats were administered intraperitoneally saline, 10 or 20 mg/kg bupropion. Upon completion, a range of nicotine and bupropion doses were assessed before substitution tests with varenicline and sazetidine-A were conducted. RESULTS: The SAL-0.4NIC and 10BUP-0.4NIC groups readily discriminated by session 8, as evidenced by increased dipper entries (goal-tracking) on nicotine days. The 20BUP-0.4NIC group was slower to acquire the discrimination. Female rats, regardless of group, had higher conditioned responding evoked by the lowest dose of nicotine (0.025 mg/kg) in the dose-effect curve. The discrimination required rats to learn to withhold responding to the training dose of bupropion. This withholding of excitatory dipper entries generalized to other doses. Varenicline and sazetidine-A partially substituted for the nicotine stimulus, and this pattern did not differ with training history. CONCLUSIONS: We are the first to study a drug-drug discrimination using the DGT task. Females appeared to have a lower discrimination threshold for nicotine that was not impacted by the learning history. Further work on the importance of sex as a biological variable and how the complex interoceptive stimulus effects of nicotine can vary with training histories is needed.


Subject(s)
Bupropion , Nicotine , Animals , Bupropion/pharmacology , Discrimination Learning , Dose-Response Relationship, Drug , Female , Goals , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Rats , Rats, Sprague-Dawley
14.
Neuropharmacology ; 202: 108845, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34678376

ABSTRACT

Nicotine enhances the rewarding effects of other environmental stimuli; this reward-enhancement encourages and maintains nicotine consumption. Nicotine use precedes other psychostimulant use, but receiving a stimulant prescription also predicts future smoking. Previously, no study has investigated effects of drug exposure order in reward-enhancement, nor with nicotine and d-amphetamine. Thus, we aimed to investigate how drug exposure order impacted the reward-enhancing effects of nicotine and d-amphetamine, alone and in combination. We used 20 male and 20 female Sprague-Dawley rats. Enhancement was investigated within-subjects by examining responding maintained by a visual stimulus reinforcer following a pre-session injection of either d-amphetamine (Sal, 0.1, 0.3, or 0.6 mg/kg) or nicotine (Sal, 0.03, 0.06, 0.1, 0.3 mg/kg). Twenty rats (10 M, 10 F) completed enhancement testing with nicotine before d-amphetamine. The other 20 rats (10 M, 10 F) completed testing with d-amphetamine before nicotine. Following these phases, rats were then given two pre-session injections: one of d-amphetamine (Sal, 0.1, 0.3, or 0.6 mg/kg) and another of nicotine (Sal, 0.03, 0.06, 0.1, or 0.3 mg/kg). Experiencing amphetamine before nicotine increased reward-enhancing effects of nicotine. Females exhibited greater effects of d-amphetamine on reward-enhancement, with no effect of exposure order. During the interaction phase, receiving nicotine before amphetamine enhanced the interaction between nicotine and d-amphetamine for females whereas amphetamine before nicotine heightened this interaction for males. From this, prior and current amphetamine use, in addition to sex, should be considered when treating nicotine dependency and when examining factors driving poly-substance use involving nicotine and d-amphetamine. Keywords: Adderall, ADHD, Dexedrine, operant, smoking, polysubstance use.


Subject(s)
Dextroamphetamine/administration & dosage , Dextroamphetamine/adverse effects , Nicotine/administration & dosage , Nicotine/adverse effects , Reinforcement, Psychology , Reward , Sex Characteristics , Animals , Conditioning, Operant , Drug Combinations , Female , Humans , Male , Rats, Sprague-Dawley , Substance-Related Disorders
15.
J Extracell Vesicles ; 10(14): e12177, 2021 12.
Article in English | MEDLINE | ID: mdl-34913274

ABSTRACT

Extracellular vesicles (EVs), which express a repertoire of cargo molecules (cf. proteins, microRNA, lipids, etc.), have been garnering a prominent role in the modulation of several cellular processes. Here, using both non-human primate and rodent model systems, we provide evidence that brain-derived EV (BDE) miRNA, miR-29a-3p (mir-29a), is significantly increased during chronic methamphetamine (MA) exposure. Further, miR-29a levels show significant increase both with drug-seeking and reinstatement in a rat MA self-administration model. We also show that EV-associated miR-29a is enriched in EV pool comprising of small EVs and exomeres and further plays a critical role in MA-induced inflammation and synaptodendritic damage. Furthermore, treatment with the anti-inflammatory drug ibudilast (AV411), which is known to reduce MA relapse, decreased the expression of miR-29a and subsequently attenuated inflammation and rescued synaptodendritic injury. Finally, using plasma from MUD subjects, we provide translational evidence that EV-miR29a could potentially serve as a biomarker to detect neuronal damage in humans diagnosed with MA use disorder (MUD). In summary, our work suggests that EV-associated miR-29a-3p plays a crucial role in MUD and might be used as a potential blood-based biomarker for detecting chronic inflammation and synaptic damage.


Subject(s)
Extracellular Vesicles/metabolism , Methamphetamine/adverse effects , MicroRNAs/adverse effects , Animals , Chronic Disease , Humans , Macaca mulatta
16.
ACS Chem Neurosci ; 12(18): 3284-3287, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34428024

ABSTRACT

While sugar consumption and alcohol drinking have traditionally been studied by different basic science fields, most commercially available flavored alcoholic beverages are sweetened with some kind of sugar. The prevailing view is that these sugars potentiate drinking by making the alcohol taste better, particularly for adolescents, overlooking that some central nervous system circuits implicated in alcohol drinking are also sensitive to brain penetrant sugars like glucose. In this Viewpoint, we highlight the need for basic researchers to carefully consider how the sugars mixed with alcoholic beverages may impact the neurochemical and biological mechanisms influencing alcohol drinking and the development of alcohol use disorder.


Subject(s)
Alcoholic Beverages , Sugars , Adolescent , Alcohol Drinking , Ethanol , Humans , Taste
17.
Behav Pharmacol ; 32(5): 435-447, 2021 08 01.
Article in English | MEDLINE | ID: mdl-34010168

ABSTRACT

Nicotine enhances the value of environmental stimuli and rewards, and reward enhancement can maintain nicotine consumption. Stimulants such as d-amphetamine are misused more by women and are commonly co-used with nicotine. d-Amphetamine potentiates nicotine's effects in human and animal research. To date, there are no published studies examining this interaction in a reward-enhancement task. The current study sought to investigate the reward-enhancing effects of nicotine alongside and coadministered with d-amphetamine. Further, we evaluated the persistence of reward enhancement across ratio and temporal schedules of reinforcement. We used 10 male and 10 female Sprague-Dawley rats. Enhancement was assessed within subjects by examining active lever pressing for a visual stimulus reinforcer on variable ratio 3, variable interval 30 s and variable time 30 s - variable ratio 3 schedules. Before 1-h sessions, rats received one injection of saline, 0.1 or 0.3 mg/kg d-amphetamine and one of saline or 0.4 mg/kg nicotine, making six possible drug combinations (saline + saline, saline + nicotine, 0.1 d-amphetamine + aline, 0.1 d-amphetamine + nicotine, 0.3 d-amphetamine + saline and 0.3 d-amphetamine + nicotine) experienced in a randomized order by each rat. When d-amphetamine was coadministered with nicotine, we found an interaction effect on reward enhancement that persisted across schedules of reinforcement. Males and females exhibited reward enhancement by 0.3 d-amphetamine, while only females showed reward enhancement by 0.1 d-amphetamine. Further, females responded more for the visual stimulus than males in all d-amphetamine conditions. Future studies should assess how reward enhancement is involved in high nicotine-amphetamine comorbidity rates and enhanced amphetamine misuse in women.


Subject(s)
Dextroamphetamine/pharmacology , Nicotine/pharmacology , Reinforcement, Psychology , Reward , Amphetamine-Related Disorders/epidemiology , Animals , Behavior, Animal/drug effects , Central Nervous System Stimulants/pharmacology , Comorbidity , Drug Synergism , Female , Humans , Male , Photic Stimulation/methods , Rats , Rats, Sprague-Dawley , Sex Factors , Tobacco Use Disorder/epidemiology
18.
Pharmacol Biochem Behav ; 201: 173089, 2021 02.
Article in English | MEDLINE | ID: mdl-33422599

ABSTRACT

Methamphetamine (meth) dependence is often characterized by persistent and chronic relapse (i.e., return to drug use). Previous work suggests females may be at greater risk to relapse. In this study, we extended this limited evidence and identified sex-dependent neural substrates related to meth-triggered reinstatement. Male and female Sprague-Dawley rats were implanted with indwelling jugular catheters. Half of the rats were then trained to self-administer meth (0.05 mg/kg/inf); the other half self-administered saline during 21 daily sessions (2 h). Rats were then given 12 extinction sessions. Twenty-four hours after the last extinction session, rats received reinstatement testing. Half of the rats received a meth-prime (0.3 mg/kg, IP) injection and the remaining rats received a saline injection. This design resulted in 4 separate groups for each sex, allowing for careful investigation of brain regions related to meth-triggered reinstatement. Brains were harvested following the reinstatement session and c-Fos immunoreactivity was measured in multiple brain regions. Meth triggered reinstatement in both sexes and this effect was more robust in females compared to males. Significant sex differences were detected. Females showed greater c-Fos immunoreactivity in the cingulate cortex area 1, lateral orbitofrontal cortex, prelimbic cortex, caudate-putamen, nucleus accumbens core and shell, and central nucleus of the amygdala following meth-primed reinstatement.


Subject(s)
Amphetamine-Related Disorders/metabolism , Amphetamine-Related Disorders/psychology , Central Nervous System Stimulants/administration & dosage , Drug-Seeking Behavior/drug effects , Methamphetamine/administration & dosage , Proto-Oncogene Proteins c-fos/metabolism , Animals , Central Amygdaloid Nucleus/metabolism , Disease Models, Animal , Extinction, Psychological , Female , Gyrus Cinguli/metabolism , Immunohistochemistry/methods , Male , Nucleus Accumbens/metabolism , Prefrontal Cortex/metabolism , Rats , Rats, Sprague-Dawley , Recurrence , Self Administration , Sex Factors
19.
Exp Clin Psychopharmacol ; 29(4): 385-394, 2021 Aug.
Article in English | MEDLINE | ID: mdl-32297785

ABSTRACT

This study was designed to assess whether nicotine can acquire additional reinforcing properties through associations with other rewards. To this end, rats self-administered nicotine-alone (0.01 mg/kg) or nicotine paired with access to sucrose during the conditioning phase. In the subsequent challenge phase, we tested the effect of nicotine-sucrose pairings on the reinforcing effects of nicotine using a progressive ratio schedule of reinforcement. Using this approach, we show that (a) rats in both paired and nicotine-alone conditions self-administered similar amounts of nicotine in the initial conditioning phase of the study when intake was limited to 10 infusions per session, (b) nicotine rapidly acquired control over goal-tracking behavior in the paired condition, (c) rats that had a history of nicotine and sucrose pairings worked harder and took more nicotine as measured on a progressive ratio using a distinct response form, and (d) conditioned goal-tracking evoked by nicotine did not show extinction when sucrose was no longer paired with nicotine over the 11 days of nicotine self-administration on a progressive ratio schedule of reinforcement. Overall, our results demonstrate that in addition to the multifaceted nature of nicotine stimulus that includes primary reinforcing effects, conditioned reinforcing effects, and reward enhancing effects, nicotine can also acquire additional reinforcing properties through associations with other rewards. This ability to acquire additional reinforcing properties through associative learning may contribute to the development and perpetuation of tobacco use disorder. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Nicotine , Reinforcement, Psychology , Tobacco Use Disorder , Animals , Conditioning, Operant , Male , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Rats , Rats, Sprague-Dawley
20.
Am Psychol ; 76(1): 154-164, 2021 01.
Article in English | MEDLINE | ID: mdl-33151699

ABSTRACT

The American Psychological Association (APA), under the oversight of the Board of Educational Affairs, and the Board of Professional Affairs, is responsible for the education and training of psychologists in prescriptive authority. All APA standards and guidelines are required by Association Rule 30-8.3 to be revised at least every 10 years. The standards for training psychologists in the safe and responsible practice of prescribing psychotropic medication have been recently updated (Model Education and Training Program in Psychopharmacology for Prescriptive Authority, APA, 2019). A departure from the 1996 and 2009 versions of that document is that training may now be conducted at the doctoral level; however, a postdoctoral supervised clinical fellowship can only occur after the attainment of licensure as a practicing psychologist. Two novel features of the 2019 revision are the use of a competency-based model of learning and assessment, and increased emphasis on supervised clinical experiences in physical assessment and medication management. By the time of completion of their fellowships, practicing psychologists are expected to have clinical competence in the measurement and interpretation of vital signs; neurological examination; therapeutic drug monitoring; systems of care; pharmacology; clinical pharmacology; psychopharmacological research; and finally, professional, ethical, and legal issues. The updated standards were approved as APA policy in February 2019. This article briefly reviews the revision process and highlights the updates made in the most recent version of the standards. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Clinical Competence , Drug Prescriptions , Psychology/education , Psychology/standards , Psychopharmacology/education , Psychopharmacology/standards , Humans , Societies, Scientific
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