Toluene alters the intrinsic excitability and excitatory synaptic transmission of basolateral amygdala neurons.

Introduction: Inhalant abuse is an important health issue especially among children and adolescents who often encounter these agents in the home. Research into the neurobiological targets of inhalants has lagged behind that of other drugs such as alcohol and psychostimulants. However, studies from our lab and others have begun to reveal how inhalants such as the organic solvent toluene affect neurons in key addiction related areas of the brain including the ventral tegmental area, nucleus accumbens and medial prefrontal cortex. In the present study, we extend these findings and examine the effect of toluene on electrophysiological responses of pyramidal neurons in the basolateral amygdala BLA, a region important for generating emotional and reward based information needed to guide future behavior. Methods: Whole-cell patch-clamp electrophysiology recordings of BLA pyramidal neurons in rat brain slices were used to assess toluene effects on intrinsic excitability and excitatory glutamatergic synaptic transmission. Results: Acute application of 3 mM but not 0.3 mM toluene produced a small but significant (~20%) increase in current-evoked action potential (AP) firing that reversed following washout of the toluene containing solution. The change in firing during exposure to 3 mM toluene was accompanied by selective changes in AP parameters including reduced latency to first spike, increased AP rise time and decay and a reduction in the fast after-hyperpolization. To examine whether toluene also affects excitatory synaptic signaling, we expressed channelrhodopsin-2 in medial prefrontal cortex neurons and elicited synaptic currents in BLA neurons via light pulses. Toluene (3 mM) reduced light-evoked AMPA-mediated synaptic currents while a lower concentration (0.3 mM) had no effect. The toluene-induced reduction in AMPA-mediated BLA synaptic currents was prevented by the cannabinoid receptor-1 antagonist AM281. Discussion: These findings are the first to demonstrate effects of acute toluene on BLA pyramidal neurons and add to existing findings showing that abused inhalants such as toluene have significant effects on neurons in brain regions involved in natural and drug induced reward.

Concentration-dependent effects of reductive pulmonary inhalants on ultrafine particle-induced oxidative stress: Insights for health risk assessment.

The impact of reductive pulmonary inhalants on ultrafine particles (UFPs)-induced pulmonary oxidative stress remains a crucial consideration, yet the concentration-dependent effects of these inhalants have remained unexplored. Here we synthesized composite UFPs simulating atmospheric UFPs, primarily composed of metals and quinones. We subjected these UFPs to varying concentrations (0-7000 µM) of two reductive pulmonary inhalants, N-acetylcysteine and salbutamol, to assess their influence on oxidative potential, measured through the dithiothreitol assay (OPDTT). Simultaneously, we analysed the soluble metal content of UFPs to uncover potential relationships between oxidative potential and metal solubility. Our results unveil a dual role played by these inhalants in shaping the OPDTT of composite UFPs. Specifically, OPDTT generally increased as inhalant concentrations rose from 0 to 300 µM. However, an intriguing reversal occurred when concentrations exceeded 500 µM, resulting in a decline in OPDTT. Relative to untreated UFPs, these inhalants induced promotion and inhibition effects within concentration ranges of 100-500 and >1000 µM, respectively. While no significant correlation emerged between OPDTT and soluble metal content as inhalant concentrations ranged from 0 to 7000 µM, noteworthy positive correlations emerged at lower inhalant concentrations (e.g., N-acetylcysteine at 0-300 µM). These findings provide insights into the potential influence of reductive pulmonary inhalants on health risks associated with UFP exposure, further underscoring the need for continued research in this critical area.

A Comparison of Dobutamine, Norepinephrine, Vasopressin, and Hetastarch for the Treatment of Isoflurane-Induced Hypotension in Healthy, Normovolemic Dogs.

Isoflurane is a commonly used inhalation anesthetic in species undergoing veterinary care that induces hypotension, impacting organ perfusion, making it imperative to minimize its occurrence or identify effective strategies for treating it. This study evaluated and compared the hemodynamic effects of DOB, NEP, VAS, and HES in twelve isoflurane-anesthetized Beagle dogs. The order of the first three treatments was randomized. HES was administered last. Data were collected before treatments (baseline) and after 10 min of a sustained MAP of <45 mmHg induced by a high end-tidal isoflurane concentration (T0). Once treatment was initiated and the target MAP was achieved (65 to 80 mmHg) or the maximum dose reached, data were collected after 15 min of stabilization (T1) and 15 min after (T2). A 15 min washout period with a MAP of ≥65 mmHg was allowed between treatments. The intravenous dosage regimens started and were increased by 50% every five minutes until the target MAP or maximum dose was reached. The dosages were as follows: DOB, 5-15 µg/kg/min; NEP, 0.1-2 µg/kg/min; VAS, 0.5-5 mU/kg/min; and HET, 6% 1-20 mL/kg/min. DOB improved CO, DO2, and VO2, but reduced SVR. VAS elevated SVR, but decreased CO, DO2, and VO2. HES minimally changed BP and mildly augmented CO, DO2, and VO2. These treatments failed to reach the target MAP. NEP increased the arterial BP, CO, MPAP, and PAWP, but reduced HR. Norepinephrine infusion at 0.44 ± 0.19 µg/kg/min was the most efficient therapy for correcting isoflurane-induced hypotension.

A brief exposure to toluene vapor alters the intrinsic excitability of D2 medium spiny neurons in the rat ventral striatum.

Although volatile organic solvents such as toluene are used for commercial and industrial uses, they are often voluntarily inhaled for their intoxicating and euphoric effects. Research into the effects of inhalants such as toluene on brain function have revealed actions on a variety of ligand-gated and voltage-activated ion channels involved in regulating neuronal excitability. Previous work from this laboratory has also shown that brief exposures to toluene vapor induce changes in the intrinsic excitability and synaptic transmission of neurons within the medial prefrontal cortex and ventral tegmental area that vary depending on projection target. In the present study, we recorded current-evoked spiking of medium spiny neurons (MSNs) in the nucleus accumbens (NAc) core and shell in adolescent rats exposed to an intoxicating concentration of toluene vapor. Compared to air controls, firing of NAc core MSNs in Sprague-Dawley rats was not altered 24 h after exposure to 10,500 ppm toluene vapor while spiking of NAc shell MSNs was enhanced at low current steps but reduced at higher current steps. When the rheobase current was used to putatively identify MSN subtypes, both "D1-like" and "D2-like" MSNs within the NAc shell but not core showed toluene-induced changes in firing. As toluene may itself have altered the rheobase resulting in misclassification of neuron subtype, we conducted additional studies using adolescent D2-Cre rats infused with a Cre-dependent mCherry reporter virus. Following toluene vapor exposure, spiking of NAc shell D2+ MSNs was enhanced at low current steps but inhibited at higher currents as compared to air controls while there were no differences in the firing of NAc shell D2- MSNs. The toluene-induced change in NAc D2+ shell MSN firing was accompanied by alterations in membrane resistance, rheobase, action potential rise time and height with no changes noted in D2- MSNs. Overall, these data add to a growing literature showing that brief exposures to intoxicating concentrations of toluene vapor causes selective alterations in the excitability of neurons within the addiction neurocircuitry that vary depending on sub-region, cell-type and projection target.

Understanding the Mechanisms of Action and Effects of Drugs of Abuse.

AIM: Drug abuse and addiction are major public health concerns, with millions of people worldwide affected by the negative consequences of drug use. To better understand this complex issue, a review was conducted to examine the mechanisms of action and effects of drugs of abuse, including their acute and chronic effects, the symptoms of abstinence syndrome, as well as their cardiovascular impacts. METHODS: The analyzed data were obtained after surveying an electronic database, namely PubMed, with no time limit, grey literature sources, and reference lists of relevant articles. RESULTS: The review highlights the different categories of drugs of abuse, such as opioids, stimulants, depressants, hallucinogens, and cannabis, and discusses the specific ways that each drug affects the brain and body. Additionally, the review explores the short-term and long-term effects of drug abuse on the body and mind, including changes in brain structure and function, physical health problems, and mental health issues, such as depression and anxiety. In addition, the review explores the effects of drug abuse on cardiovascular health, focusing on electrocardiogram changes. Moreover, the analysis of relevant literature also highlighted possible genetic susceptibility in various addictions. Furthermore, the review delves into the withdrawal symptoms that occur when someone stops using drugs of abuse after a period of chronic use. CONCLUSION: Overall, this review provides a comprehensive overview of the current state of knowledge on drug abuse and addiction. The findings of this review can inform the development of evidence-based prevention and intervention strategies to address this critical public health issue.

Cognitive, imaging, and psychiatric changes associated with chronic toluene use: case report and literature review.

Inhalant misuse and inhalant use disorder are global public health concern that impacts adolescents but can occur throughout life. Toluene is the most commonly misused inhalant. Toluene use leads to significant neuroanatomic, cognitive, and psychiatric deficits. The purpose of this study was to review and summarize the effects of toluene and present a case of a middle-aged patient with an inhalant use disorder. A literature review was conducted to evaluate imaging, neurocognitive, and psychiatric consequences of toluene misuse. The common imaging findings amongst those who misuse toluene were cerebral and cerebellar atrophy, ventricular dilation, loss of gray-white matter differentiation, corpus callosum thinning, and diffuse white matter changes. Concerning cognition, toluene misusers were shown to have deficits in intelligence, attention, memory, visuospatial function, and complex cognition. In addition, toluene users also commonly presented with apathy, flat affect, hallucinations, delusions, anxiety, depression, and insomnia. The neuroanatomical, neurocognitive, and psychiatric effects of toluene misuse are profound. These deficits can make inhalant use disorder difficult to treat. Therefore, evidence-based treatments that recognize and address these domain-specific neurocognitive deficits are needed.

Syncope and Methemoglobinemia Preceded by Amyl Nitrite 'Popper' Inhalation.

INTRODUCTION: Methemoglobinemia represents an uncommon but potentially serious cause of presentation to the emergency department, resulting in hypoxemia and even death. The symptoms and clinical findings in this condition can be nonspecific and therefore methemoglobinemia can be easily missed if the clinician is not familiar with it. This report presents a case caused by recreational drug use which has rarely been documented previously. CASE REPORT: A 23-year-old male with a history of asthma presents to the emergency department for an episode of syncope after inhalation of amyl nitrite "poppers". He had normal vitals other than tachycardia but was found to have nailbed and perioral cyanosis, a classic but uncommon presentation that is demonstrated in the included clinical image. He was found to have methemoglobinemia caused by his use of amyl nitrite and received supportive care but did not require methylene blue. CONCLUSION: Emergency physicians should familiarize themselves with the classic physical exam findings in methemoglobinemia in order to identify and treat this condition promptly. While this patient had a good outcome with only supportive care and observation, his presentation and the etiology of his condition offer an important teaching point. The possibility of methemoglobinemia after recreational "popper" use should be considered when working up a patient who presents with cyanosis and hypoxemia.

Toward a typology of driving under the influence of alcohol and drugs.

PURPOSE: Most research on driving under the influence (DUI) has relied upon variable-centered methods that examine predictors/correlates of DUI. In the present study, we utilize a person-level approach-latent class analysis (LCA)-to model a typology of individuals reporting DUI. This allows us to understand the degree to which individuals drive under the influence of a particular substance or do so across multiple substance types. METHODS: We use public-use data collected between 2016 and 2019 from the National Survey on Drug Use and Health. The analytic sample was 189,472 participants with a focus on those reporting DUI of psychoactive substances in the past-year (n = 24,619). LCA was conducted using self-reported DUI of past-year alcohol, cannabis, cocaine, heroin, hallucinogens, and methamphetamine as indicator variables. RESULTS: More than 1 in 10 Americans reported a DUI within the past-year. One in five people who reported DUI of one substance also reported DUI of at least one additional substance. Using LCA to model heterogeneity among individuals reporting DUI, four classes emerged: "Alcohol Only" (55%), "Cannabis and Alcohol" (36%), "Polydrug" (5%), and "Methamphetamine" (3%). Rates of risk propensity, drug involvement, illicit drug use disorders, and criminal justice system involvement were highest among members of the "Polydrug" and "Methamphetamine" classes. CONCLUSION: Drug treatment centers should take care to include discussions of the dangers and decision-making processes related to DUI of the full spectrum of illicit substances. Greater investment in drug treatment across the service continuum, including the justice system, could prevent/reduce future DUI episodes.

Examining Inhalant Use Among Sexual Minority Adults in a National Sample: Drug-Specific Risks or Generalized Risk?

Purpose: The study objective was to compare use of 12 specific inhalants among lesbian, gay, and bisexual (LGB) adults relative to heterosexual adults among a national sample. Methods: Data on 210,392 adults, including 15,007 LGB adults, were from the 2015 to 2019 National Survey on Drug Use and Health. For each inhalant type, logistic regression was used to characterize differences by sexual identity and gender. Unadjusted and demographic adjusted odds ratios are reported. Results: All LGB groups exhibited elevated use of multiple inhalant types (ranging from 5 for gay males to 12 for bisexual females). The largest disparities were for poppers among gay and bisexual males. Gay and bisexual males initiated use at older ages. Conclusion: Observed disparities among LGB adults included inhalants used in a sexual or club context (e.g., poppers) as well as types with particularly elevated fatality risk (e.g., butane, propane, aerosol sprays, and nitrous oxide).

Rare case of chronic naphthalene ball ingestion in a young Indian woman.

Chronic oral abuse of naphthalene balls is extremely rare. It is associated with different types of metabolic toxicity, neurological deficits and multiple organ failure. However, the psychological implication of naphthalene abuse is poorly understood. This is a unique case report of a 29-year-old lady who presented with a 17 year history of naphthalene ball consumption. Historically, there have been self-harm behaviors, fire setting, cleaning compulsions, and involuntary motor movements associated with naphthalene. A series of assessments were conducted to assess her personality, psychiatric symptoms and cognitive functions. Additionally, blood tests, CT scan and MRI were done. The patient's profile indicated no apparent medical, neurological or cognitive impairments. Her psychological profile revealed significant co-morbidities and marked personality pathology. The case study provides useful insights into the presentation of chronic naphthalene ball ingestion in an Indian woman, thereby indicating the need to identify psychosocial and biological markers longitudinally. It also highlights recognition of common household items that can be abused, suggesting better understanding of protecting vulnerable individuals from the same.

Biological effects of inhaled crude oil vapor V. Altered biogenic amine neurotransmitters and neural protein expression.

Workers in the oil and gas industry are at risk for exposure to a number of physical and chemical hazards at the workplace. Chemical hazard risks include inhalation of crude oil or its volatile components. While several studies have investigated the neurotoxic effects of volatile hydrocarbons, in general, there is a paucity of studies assessing the neurotoxicity of crude oil vapor (COV). Consequent to the 2010 Deepwater Horizon (DWH) oil spill, there is growing concern about the short- and long-term health effects of exposure to COV. NIOSH surveys suggested that the DWH oil spill cleanup workers experienced neurological symptoms, including depression and mood disorders, but the health effects apart from oil dispersants were difficult to discern. To investigate the potential neurological risks of COV, male Sprague-Dawley rats were exposed by whole-body inhalation to COV (300 ppm; Macondo surrogate crude oil) following an acute (6 h/d × 1 d) or sub-chronic (6 h/d × 4 d/wk. × 4 wks) exposure regimen. At 1, 28 or 90 d post-exposure, norepinephrine (NE), epinephrine (EPI), dopamine (DA) and serotonin (5-HT) were evaluated as neurotransmitter imbalances are associated with psychosocial-, motor- and cognitive- disorders. Sub-chronic COV exposure caused significant reductions in NE, EPI and DA in the dopaminergic brain regions, striatum (STR) and midbrain (MB), and a large increase in 5-HT in the STR. Further, sub-chronic exposure to COV caused upregulation of synaptic and Parkinson's disease-related proteins in the STR and MB. Whether such effects will lead to neurodegenerative outcomes remain to be investigated.

Management of Toxicological Emergencies in the School Setting: An Overview for School Nurses Part 2.

School nurses may encounter a variety of poisoning and overdose scenarios in the school setting. Youth have an increased risk for harm due to factors associated with substance use, self-harm, and exposure to more toxic ingestants. Poison Control Centers are uniquely qualified to assist the public and health professionals, including school nurses, with poisoning and overdose incidents and are available 24 hours per day. This article is Part 2 of a series of three articles and focuses on poisonings related to substances of abuse and addiction or as a result of social media challenges. Information includes expected clinical effects, potential for serious injury, and a reasonable approach to manage these exposures for the following substances of potential harm: alcohol, caffeine, dextromethorphan, inhalants, marijuana, tobacco, and nicotine replacement therapy. Part 3 of the series will discuss potential environmental hazards specific to the school setting.

Captopril and losartan attenuate behavioural sensitization in mice chronically exposed to toluene.

Inhalants are consumed worldwide for recreational purposes. The main component found in many inhalants is toluene. One of the most deleterious behavioural effects caused by chronic exposure to inhalants is addiction. This response has been associated with activation of the mesolimbic dopaminergic pathway, and it is known that the renin angiotensin system plays a role in the modulation of this dopaminergic system. In the present work, we hypothesize that blockade of the RAS with angiotensin converting enzyme inhibitors or angiotensin II type 1 receptor blockers is able to attenuate the addictive response induced by toluene. We exposed mice to toluene for four weeks to induce locomotor sensitization. In the second phase of the work, captopril or losartan were administered for 20 days. Subsequently, the expression of behavioural sensitization was evaluated with a toluene challenge. To exclude false associations between the observed responses and treatments, motor coordination and blood pressure were analysed in animals treated with captopril or losartan. At the end of the behavioural studies, animal brains were harvested and Ang II/Ang-(1-7) and Ang-(1-7)/Ang II ratios were analysed in the nucleus accumbens (NAc) and prefrontal cortex (PFCx). The results showed that toluene induced behavioural sensitization, while captopril or losartan treatment attenuated the expression of this response. No significant differences were observed in motor coordination or blood pressure. Repeated toluene administration decreased Ang-(1-7)/Ang II ratio in the PFCx. On the other hand, treatment with captopril or losartan decreased the Ang II/Ang-(1-7) ratio and enhanced the Ang-(1-7)/Ang II ratio in the NAc. This work suggests that blockade of RAS attenuates the toluene-induced behavioural sensitization.

Women as users and dealers of inhalants in the streets of Mexico city: A study on empowerment, cooperation, and trust at the margins.

INTRODUCTION: People who live on the streets in Mexico commonly use inhalants to induce psychoactive effects. Research on the distribution, sale, and consumption of these substances is scarce and mostly focuses on men, which limits the understanding of their use and possible public policies. Our ethnographic research concentrates on women who live and work on the street under marginalized conditions in Mexico City. METHODS: A Grounded Theory approach was used to frame the two-year-long field work. A field diary was kept for the multi-sited ethnography and participant observations in street-based settings, as well as five in-depth interviews with female distributors, sellers, and/or users of inhalants. Data was analyzed based on four dimensions: biography, representation as a dealer or user, social dynamics, and geographical distribution of networks to distribute, sell, and use inhalants. RESULTS: Women involved in the distribution, sale and use of inhalants are motivated by gender violence and socioeconomic vulnerability. They shape reciprocity networks to purchase inhalants in dangerous urban areas and avoid being mugged and physically or sexually assaulted. Although men are the ones who offer protection, women employ women to sell the inhalants and strengthen trust in the community. Distribution begins in clandestine places where combinations of unknown solvents are prepared in 20-L containers. Each liter is supplied for 1.92 USD to be retailed in 9.58 USD per liter in the streets. Particular language and cultural street-codes are necessary conditions in distribution and sales points for safe use and protection from authorities and out-group members. CONCLUSION: Trust and cooperation are crucial in reciprocity networks formed by women who distribute, sell and use inhalants in the streets. These networks compensate for the lack of social security and safety, empower women in the street community, and provide income needed to survive marginality.

The last two decades on preclinical and clinical research on inhalant effects.

This paper reviews the scientific evidence generated in the last two decades on the effects and mechanisms of action of most commonly misused inhalants. In the first section, we define what inhalants are, how they are used, and their prevalence worldwide. The second section presents specific characteristics that define the main groups of inhalants: (a) organic solvents; (b) aerosols, gases, and volatile anesthetics; and (c) alkyl nitrites. We include a table with the molecular formula, structure, synonyms, uses, physicochemical properties and exposure limits of representative compounds within each group. The third and fourth sections review the direct acute and chronic effects of common inhalants on health and behavior with a summary of mechanisms of action, respectively. In the fifth section, we address inhalant intoxication signs and available treatment. The sixth section examines the health effects, intoxication, and treatment of nitrites. The seventh section reviews current intervention strategies. Finally, we propose a research agenda to promote the study of (a) solvents other than toluene; (b) inhalant mixtures; (c) effects in combination with other drugs of abuse; (d) age and (e) sex differences in inhalant effects; (f) the long-lasting behavioral effects of animals exposed in utero to inhalants; (g) abstinence signs and neurochemical changes after interrupting inhalant exposure; (h) brain networks involved in inhalant effects; and finally (i) strategies to promote recovery of inhalant users.

Preference of inhalants over pills/injections among pulmonary tuberculosis patients in Western India: A cross-sectional study.

BACKGROUND: Presently, pills and injections are the two modes of therapeutic treatment available for tuberculosis (TB) patients. Many researchers have hypothesized inhalation drug delivery for reducing treatment times and possibly limiting the insurgence of drug resistance. This study was aimed at identifying and assessing the preferences of inhalation therapy over injections/pills among pulmonary TB patients. METHOD: Cross-sectional study design was used and a sample of 477 participants were recruited at selected three Directly Observed Treatment Short-Course (DOTS) centers in Bhiwandi city. Data was collected through self-reported questionnaire. Descriptive statistics were reported, and binomial regression models were applied for data analysis. RESULTS: The preference of inhalants over pills/injections among pulmonary TB patients was significantly associated with clinical characteristics. The patients who underwent treatment for more than 1 year were 1.7 times more likely to prefer inhalants over pills/injections when compared with treatment duration of less than 1 year. Similarly, patients taking five or more pills/day were 1.7 times more likely to prefer inhalants over pills/injections when compared with patients taking 1-4 pills per day. CONCLUSION: The study results signify that inhalants could be an acceptable method of drug delivery in this population of TB patients. Diverse drug delivery options for TB patients may greatly contribute towards TB treatment adherence.

In Ovo Testing Method for Inhalants on a Chorio-Allantoic Membrane.

Solid tumors and metastasis rely on angiogenesis for sufficient supply as they grow, making antiangiogenic treatment a promising option in the combat of cancer. Testing of inhalants on the chorio-allantoic membrane offers a simple but precise method to assess the impact on angiogenesis. The in ovo testing method can be used to directly determine the effect of inhaled formulations solely or in the context of photodynamic therapy. In this study curcumin liposomes served as a model for testing of pulmonary application and revealed an excellent antiangiogenetic effect. This efficacy of a model inhalant illustrates the suitability of the method.

Differences in use of inhalants among sexual minorities in the USA in 2015-2018.

OBJECTIVES: Inhalants are substances with underestimated abuse potential associated with cardiac problems, dizziness, seizures, and decreased level of consciousness. Inhalants are commonly used by the LGB population, who are vulnerable to their harms. US epidemiologic inhalants data are scarce. The aims of this study are to: i) investigate associations between inhalant use and sexual identity groups; ii) examine associations with use of other drugs among lesbian/gays who use inhalants. METHODS: Data came from the 2015-2018 NSDUH (n = 168,560). Participants ages 18 or older were asked if they had used any inhalants in their lifetime and past-year. We investigated the associations between inhalant use with sexual identity categories heterosexual, lesbian/gay, and bisexual using logistic regression models with complex survey design. RESULTS: Total prevalences of lifetime and past-year use of inhalants were 9.4% and 0.5%, respectively. Lesbian/gay population (L/G) and bisexuals (B) reported higher odds of lifetime (L/G: aOR = 3.71, 95%CI = [3.19,4.30], B: aOR = 1.82, 95%CI = [1.64,2.03) and past-year (L/G: aOR = 11.57, 95%CI = [8.95,14.96], B: aOR = 2.81, 95%CI = [2.02,3.92]) inhalant use compared to heterosexuals. Among L/G, men had higher odds of lifetime (aOR = 4.11, 95%CI = [3.06,5.52]) and past-year (aOR = 15.67, 95%CI = [7.27,33.76]) inhalant use versus women. Use of marijuana (aOR = 2.76, 95%CI = [1.48,5.16]), other illegal drugs (aOR = 2.70, 95%CI = [1.60,4.56]), and non-medical use of psychotherapeutics (aOR = 2.67, 95%CI = 1.77,4.05) were associated with past-year use of inhalants among L/G. CONCLUSION: LGB population is at elevated risk of inhalant use and of concurrent use with other drugs. Gay men had significantly higher odds of inhalant use compared to lesbians and bisexuals. Informative and in-site harm reduction measures are warranted to prevent harms from inhalant use.

Self-Administration of Toluene Vapor in Rats.

Inhalants, including volatile organic solvents such as toluene, continue to be one of the most prevalent, and often first substances abused by adolescents. Like other drugs of abuse, toluene affects the function of neurons within key brain reward circuits including the prefrontal cortex, ventral tegmental area, and nucleus accumbens. However, preclinical models used to study these toluene-induced adaptations generally employ passive exposure paradigms that do not mirror voluntary patterns of solvent exposure observed in humans. To address this shortcoming, we developed an inhalation chamber containing active and inactive nose pokes, cue lights, flow-through vaporizers, and software-controlled valves to test the hypothesis that rats will voluntarily self-administer toluene vapor. Following habituation and self-administration (SA) training rats achieve vapor concentrations associated with rewarding effects of toluene, and maintain responding for toluene vapor, but not for air. During extinction trials, rats showed an initial burst of drug-seeking behavior similar to that of other addictive drugs and then reduced responding to Air SA levels. Responding on the active nose poke recovered during cue-induced reinstatement but not following a single passive exposure to toluene vapor. The results from these studies establish a viable toluene SA protocol that will be useful in assessing toluene-induced changes in addiction neurocircuitry.