Abuse-like toluene exposure during early adolescence alters subsequent ethanol and cocaine behavioral effects and brain monoamines in male mice.

Currently, there is a gap in understanding the neurobiological impact early adolescent toluene exposure has on subsequent actions of other drugs. Adolescent (PND 28-32) male Swiss-Webster mice (N = 210) were exposed to 0, 2000, or 4000 ppm of toluene vapor for 30 min/day for 5 days. Immediately following the last toluene exposure (PND 32; n = 15) or after a short delay (PND 35; n = 15), a subset of subjects' brains was collected for monoamine analysis. Remaining mice were assigned to one of two abstinence periods: a short 4-day (PND 36) or long 12-day (PND 44) delay after toluene exposure. Mice were then subjected to a cumulative dose response assessment of either cocaine (0, 2.5, 5, 10, 20 mg/kg; n = 60), ethanol (0, 0.5, 1, 2, 4 g/kg; n = 60), or saline (5 control injections; n = 60). Toluene concentration-dependently increased locomotor activity during exposure. When later challenged, mice exposed previously to toluene were significantly less active after cocaine (10 and 20 mg/kg) compared to air-exposed controls. Animals were also less active at the highest dose of alcohol (4 g/kg) following prior exposure to 4000 ppm when compared to air-exposed controls. Analysis of monoamines and their metabolites using High Pressure Liquid Chromatography (HPLC) within the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum (dSTR), and ventral tegmental area (VTA) revealed subtle effects on monoamine or metabolite levels following cumulative dosing that varied by drug (cocaine and ethanol) and abstinence duration. Our results suggest that early adolescent toluene exposure produces behavioral desensitization to subsequent cocaine-induced locomotor activity with subtle enhancement of ethanol's depressive effects and less clear impacts on levels of monoamines.

Childhood Violence Exposure Predicts High Blood Pressure in Black American Young Adults.

OBJECTIVE: To test the impact of childhood adversity, including community violence exposure, on hypertension risk in Black American young adults to understand what risk factors (eg, prenatal factors, later exposures) and ages of adversity exposure increased hypertension risk. STUDY DESIGN: The study included 396 Black American participants with data from prenatal, birth, and age 7-, 14-, and 19-year visits. At age 19 years, individuals with blood pressure (BP) measures >120 mmHg systolic and/or >80 mmHg diastolic were classified as having high blood pressure (HBP), and those with BP <120/80 mmHg were classified as normal. Associations between prenatal and birth risk factors; childhood adversity at age 7, 14, and 19 years; age 19 body mass index (BMI); and both systolic and diastolic BP at age 19 were tested using logistic regression models. RESULTS: Age 19 BMI was positively associated with systolic and diastolic HBP status at age 19. Controlling for all covariates, community violence exposure at age 7 and 19 years was associated with 2.2-fold (95% CI, 1.242-3.859) and 2.0-fold (95% CI, 1.052-3.664) greater odds of systolic HBP, respectively, at age 19 years. Prenatal risk, birth risk, and other dimensions of childhood adversity were not associated with HBP in this cohort. CONCLUSION: Childhood community violence exposure is a significant risk factor for HBP in young adults. As Black American children typically experience more community violence exposure than other American children, our results suggest that racial disparities in childhood community violence exposure may contribute to racial disparities in adult hypertension burden.

A novel preclinical model of environment-like combined benzene, toluene, ethylbenzene, and xylenes (BTEX) exposure: Behavioral and neurochemical findings.

Environmental exposure to toxicants is a major health issue and a leading risk factor for premature mortality worldwide, including environmental exposures to volatile organic compounds (VOCs), specifically Benzene, Toluene, Ethylbenzene, and Xylene (BTEX). While exposure to these compounds individually has shown behavioral and neurochemical effects, this investigation examined the impact of exposure to combined BTEX using a preclinical model. Male Swiss Webster mice were exposed to BTEX vapors designed to approximate environmental levels in urban communities. Animals were exposed to one of four treatment conditions: a 0-ppm (air control), two BTEX groups representing levels of environmental-like exposure, and a fourth group modeling occupational-like exposure. These exposures were conducted in 1.5-h sessions, 2 sessions/day, 5 days/week, for 3 weeks. Effects on coordination (i.e., rotarod and inverted screen test), learning and memory (i.e., Y-maze), and locomotor behavior (i.e., movement during exposure) were assessed during and after exposure. Monoamine levels in the medial prefrontal cortex and nucleus accumbens were assessed immediately following exposure. Effects of BTEX exposure were found on the variance of locomotor activity but not in other behavioral or neurochemical assessments. These results indicate that the combination of inhaled BTEX at environmentally representative concentrations has demonstrable, albeit subtle, effects on behavior.

Effects of inhaled combined Benzene, Toluene, Ethylbenzene, and Xylenes (BTEX): Toward an environmental exposure model.

Combined environmental exposures to the volatile organic compounds (VOCs) Benzene, Toluene, Ethylbenzene, and Xylene (BTEX) pose clear risks to public health. Research into these risks is under-studied even as BTEX levels in the atmosphere are predicted to rise. This review focuses on the available literature using single- and combined-BTEX component inhaled solvent exposures in animal models, necessarily also drawing on findings from models of inhalant abuse and occupational exposures. Health effects of these exposures are discussed for multiple organ systems, but with particular attention on neurobehavioral outcomes such as locomotor activity, impulsivity, learning, and psychopharmacological responses. It is clear that animal models have significant differences in the concentrations, durations and patterns of exposure. Experimental evidence of the deleterious health and neurobehavioral consequences of exposures to the individual components of BTEX were found, but these effects were typically assessed using concentrations and exposure patterns not characteristic of environmental exposure. Future studies with animal models designed appropriately to explore combined BTEX will be necessary and advantageous to discovering health outcomes and more subtle neurobehavioral impacts of long-term environmental exposures.

Violence exposure, conflict, and health outcomes in inner-city African American adolescents.

PURPOSE: To examine relationships among community and school violence exposure, parent-adolescent conflict, coping style, and self-reported health in a sample of 432 high-risk, inner-city African American adolescents at age 14 years. DESIGN AND METHODS: Multiple regression and principal component analysis were used to analyze the secondary data. After controlling for multiple covariates (eg, sex, age, blood lead levels, and socioeconomic status), both violence exposure and posttraumatic stress symptoms (PTSS) were related to health outcomes. The survey of exposure to community violence, the safe-school survey, and the conflict tactics scale were used to measure community violence, school violence, and parent-adolescent conflict. Coping was evaluated using the general coping scale. The child health illness profile-adolescent edition was used to obtain self-reported health measures, and the clinician-assisted PTSD scale was used to measure PTSS. RESULTS: Higher exposure to community violence was associated with less emotional comfort, less family involvement, higher individual risk, and poorer academic and work performance. Parent-adolescent conflict predicted less physical and emotional comfort and poorer home safety and health. CONCLUSIONS: Our findings suggest that it is important to evaluate both violence exposure and the responses to the exposure, which can include both PTSS and diverse coping strategies.

Prenatal Alcohol Screening During Pregnancy by Midwives and Nurses.

BACKGROUND: Alcohol use during pregnancy can have a variety of harmful consequences on the fetus. Lifelong effects include growth restriction, characteristic facial anomalies, and neurobehavioral dysfunction. This range of effects is known as fetal alcohol spectrum disorders (FASD). There is no amount, pattern, or timing of alcohol use during pregnancy proven safe for a developing embryo or fetus. Therefore, it is important to screen patients for alcohol use, inform them about alcohol's potential effects during pregnancy, encourage abstinence, and refer for intervention if necessary. However, how and how often nurses and midwives inquire about alcohol drinking during pregnancy or use recommended screening tools and barriers they perceive to alcohol screening has not been well established. METHODS: This survey was sent to about 6,000 American midwives, nurse practitioners, and nurses who provide prenatal care about their knowledge of the effects of prenatal alcohol exposure, the prevalence of alcohol use during pregnancy, and practices for screening patients' alcohol use. Participants were recruited by e-mail from the entire membership roster of the American College of Nurse-Midwives. RESULTS: There were 578 valid surveys returned (about 9.6%). Analyses showed that 37.7% of the respondents believe drinking alcohol is safe during at least one trimester of pregnancy. Only 35.2% of respondents reported screening to assess patient alcohol use. Only 23.3% reported using a specific screening tool, and few of those were validated screens recommended for use in pregnant women. Respondents who believe alcohol is safe at some point in pregnancy were significantly less likely to screen their patients. CONCLUSIONS: Respondents who reported that pregnancy alcohol use is unsafe felt more prepared to educate and intervene with patients regarding alcohol use during pregnancy and FASD than respondents who reported drinking in pregnancy was safe. Perceived alcohol safety and perceived barriers to screening appeared to influence screening practices. Improving prenatal care provider knowledge about the effects of prenatal alcohol exposure and the availability of valid alcohol screening tools will improve detection of drinking during pregnancy, provide more opportunities for meaningful intervention, and ultimately reduce the incidence of FASD.

Abstinence following toluene exposure increases anxiety-like behavior in mice.

The intentional misuse of volatile solvents like toluene is a persistent public health concern. Limited clinical data suggest that chronic inhalant abusers may experience signs of withdrawal, including anxiety. Behavioral withdrawal from toluene has not been examined in a preclinical model. In the current study, young adult male Swiss Webster mice were exposed to either 5000-ppm toluene vapor or air (0ppm) for 30min or 24h. Mice were tested in a battery of four behavioral tasks reflective of anxiety either immediately (0h), 24h, or 72h after the toluene exposure. Mice exposed briefly (30min) to toluene showed decreases in anxiety-like behaviors, whereas mice abstinent from toluene for 24h after a prolonged (24-h) exposure, displayed increases in anxiety-like behaviors. These increases in anxiety-like behavior were not observed 72h post toluene. However, a brief re-exposure to toluene (30min at 5000ppm) immediately before testing 24h after the prolonged exposure ameliorated behavioral differences on the plus maze task. These results of 1) decreased anxiety-like behavior immediately following acute toluene, and 2) the contrasting increase in anxiety-like behavior during abstinence from a prolonged toluene exposure, and 3) the amelioration of increases in an anxiety-like behavior following toluene re-exposure, are consistent with an interpretation of withdrawal from the single 24-hr toluene exposure. These findings support clinical reports of increased anxiety during abstinence following periods of toluene use/abuse. The results also imply that experiencing anxiety during withdrawal from toluene may contribute to the persistent use of inhalants and may be relevant to clinical treatment of inhalant abuse/addiction.

Prenatal alcohol exposure selectively enhances young adult perceived pleasantness of alcohol odors.

Prenatal alcohol exposure (PAE) can lead to life-long neurobehavioral and social problems that can include a greater likelihood of early use and/or abuse of alcohol compared to older teens and young adults without PAE. Basic research in animals demonstrates that PAE influences later postnatal responses to chemosensory cues (i.e., odor & taste) associated with alcohol. We hypothesized that PAE would be related to poorer abilities to identify odors of alcohol-containing beverages, and would alter perceived alcohol odor intensity and pleasantness. To address this hypothesis we examined responses to alcohol and other odors in a small sample of young adults with detailed prenatal histories of exposure to alcohol and other drugs. The key finding from our controlled analyses is that higher levels of PAE were related to higher relative ratings of pleasantness for alcohol odors. As far as we are aware, this is the first published study to report the influence of PAE on responses to alcohol beverage odors in young adults. These findings are consistent with the hypothesis that positive associations (i.e., "pleasantness") to the chemosensory properties of alcohol (i.e., odor) are acquired prenatally and are retained for many years despite myriad interceding postnatal experiences. Alternate hypotheses may also be supported by the results. There are potential implications of altered alcohol odor responses for understanding individual differences in initiation of drinking, and alcohol seeking and high-risk alcohol-related behaviors in young adults.

Parental Support, Mental Health, and Alcohol and Marijuana Use in National and High-Risk African-American Adolescent Samples.

African-American adolescents experience disproportionate rates of negative consequences of substance use despite using substances at average or below-average rates. Due to underrepresentation of African-American adolescents in etiological literature, risk and protective processes associated with their substance use require further study. This study examines the role of parental support in adolescents' conduct problems (CPs), depressive symptoms (DSs), and alcohol and marijuana use in a national sample and a high-risk sample of African-American adolescents. In both samples, parental support was inversely related to adolescent CPs, DSs, and alcohol and marijuana use. CPs, but not DSs, partially mediated the relation of parental support to substance use. Results were consistent across the national and high-risk samples, suggesting that the protective effect of parental support applies to African-American adolescents from a range of demographic backgrounds.

Increased cut-point of the TACER-3 screen reduces false positives without losing sensitivity in predicting risk alcohol drinking in pregnancy.

BACKGROUND: Detection of in-pregnancy maternal risk alcohol drinking is an essential first step in preventing fetal alcohol spectrum disorders, and the widely used T-ACE screen was developed for that purpose. We recently reported that increasing the total T-ACE score cut-point from 2 to 3 doubled specificity of detecting risk drinking in pregnancy and identified 4-year-old children with neurobehavioral effects associated with prenatal alcohol exposure. METHODS: In this study, the TACER-3 was further validated in another prospectively identified high-risk urban cohort. Women were categorized as follows: (i) Not At-Risk Group (negative on T-ACE and TACER-3); (ii) At-Risk Group (positive on T-ACE and TACER-3); and (iii) Change Risk Group (positive on T-ACE but negative on TACER-3). RESULTS: The TACER-3 total score cut-point of 3 yielded fewer "false positives" than the T-ACE cut-point of 2. Based on relative risk scores, women in the TACER-3-positive At-Risk Group were more likely to drink alcohol during pregnancy than women in the Change Risk Group. In contrast, women in the Not At-Risk Group were largely not different in their drinking from women in the Change Risk Group. The largest increases in relative risk of the At-Risk Group compared to the Change Risk Group were for the amount of drinking per day across pregnancy (RR = 11.4) and for the amount of drinking per drinking day at the first prenatal visit (RR = 12.7). For both of these measures, the relative risk of at-risk alcohol consumption in the At-Risk Group was over >10 times that of the Change Risk Group. CONCLUSIONS: Thus, the TACER-3 was more effective at selectively identifying women drinking at fetal risk levels than the original T-ACE. The TACER-3 allows for more efficient use of healthcare provider time in directing targeted clinical interventions with pregnant women identified as drinking at fetal risk levels.

Binge toluene exposure in pregnancy and pre-weaning developmental consequences in rats.

Binge Toluene Exposure in Pregnancy and Pre-weaning Developmental Consequences in Rats. Bowen, S.E. and Hannigan, J.H. The persistent rate of abuse of inhaled organic solvents, especially among women of child-bearing age, raises the risk for teratogenic effects of maternal toluene abuse. In this study, timed-pregnant Sprague Dawley rats were exposed from Gestation Day (GD) 8 to GD20 to 12,000 or 8000 parts per million (ppm) toluene, or 0ppm (controls) for 30min twice daily, 60min total daily exposure. Pups were assessed from postnatal day (PN) 4 to PN21 using a developmental battery measuring growth (i.e., body weight), maturational milestones (e.g., eye opening & incisor eruption), and biobehavioral development (e.g., negative geotaxis & surface righting). Pups exposed in utero to 12,000ppm or 8000ppm toluene weighed significantly less than the non-exposed control pups beginning at PN4 and PN12 (respectively) until PN21. Toluene resulted in significant increases in an index of poor perinatal outcome, specifically a composite of malformations, defined "runting" and neonatal death. No significant delays were observed in reaching maturational milestones. The results reveal that brief, repeated, prenatal exposure to high concentrations of toluene can cause growth retardation and malformations in rats. A comparison of the present, conservative results with findings in previous studies implies that binge patterns of toluene exposure in pregnant rats modeling human solvent abuse can result in developmental and morphological deficits in offspring. These results do not exclude the possibility that maternal toxicity as well as teratogenic effects of toluene may contribute to outcomes. The results suggest that abuse of inhaled organic solvents like toluene may result in similar early developmental outcomes in humans.

Recognized spontaneous abortion in mid-pregnancy and patterns of pregnancy alcohol use.

Alcohol consumption during pregnancy is one potential risk factor for spontaneous abortion (SAb). Prior research suggested that heavy drinking during pregnancy was associated with significantly increased rates of SAb, but results for lower levels of drinking have been inconsistent. We examined the association between different levels and patterns of prenatal alcohol consumption and SAb in a high-risk inner-city sample. We hypothesized that higher levels, binge patterns, and more frequent drinking would be associated with increased rates of SAb. The quantity and frequency of self-reported peri-conceptional and repeated in-pregnancy maternal drinking volumes per beverage type were assessed with semi-structured interviews in a prospective subsample of 302 African-American mothers. Relations between various measures of prenatal alcohol exposure and SAb were assessed using logistic regression. After controlling for various potential confounders, there was a significant positive relation between average absolute alcohol use per day across pregnancy and SAb. Greater frequency of drinking episodes also predicted SAb: an average of even one day of drinking per week across pregnancy was associated with an increase in the incidence of SAb. However, contrary to our hypothesis, neither the amount of alcohol drunk per drinking day nor a measure of binge drinking was significantly related to SAb after controlling for confounders. Differences in when women who drank at risk levels initiated antenatal care may have under-estimated the impact of alcohol on SAb in this low-SES urban African-American sample. Some drinking measures averaged across pregnancy may have under-estimated consumption and overestimated risk of SAb, but other risk drinking measures that avoid this limitation show similar relations to SAb. Identifying fetal risk drinking in pregnant women is critical to increasing the effectiveness of interventions that reduce risk level alcohol consumption and protect from pregnancy loss.

Cytokines reduce toxic effects of ethanol on oligodendroglia.

To characterize immunomodulatory mechanisms that affect oligodendroglia (OL) and white matter following ethanol exposure during early CNS development, we investigated the direct effects of ethanol and cytokines on glia. Mixed glial cultures from newborn rat brain were exposed to 6.5-130 mM ethanol for 1-3 days. OL were sensitive to ethanol, with death ranging from 32 to 88% with increasing time and ethanol concentrations. Little cell death occurred in astroglia or microglia. Mixtures of cytokines representative of those produced by pro-inflammatory Th1 and monocyte/macrophage (M/M) cells as well as those produced by anti-inflammatory Th2 cells were all protective. Three of the cytokines in the Th1 mixture, IL-2, TNF-α and IFN-γ, were protective individually, although no single cytokine was as effective as the mixture. The protective effects of the Th1 mixture and of IL-2 were reversed by inhibition of both MAP kinase and PI-3 kinase signaling pathways. We conclude that cytokines can act either directly on OL or indirectly through effects on astroglia or microglia to protect OL from ethanol toxicity.

Prenatal and postnatal cocaine exposure predict teen cocaine use.

Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use.

Binge toluene exposure alters glutamate, glutamine and GABA in the adolescent rat brain as measured by proton magnetic resonance spectroscopy.

Despite the high incidence of toluene abuse in adolescents, little is known regarding the effect of binge exposure on neurochemical profiles during this developmental stage. In the current study, the effects of binge toluene exposure during adolescence on neurotransmitter levels were determined using high-resolution proton magnetic resonance spectroscopy ex vivo at 11.7T. Adolescent male Sprague-Dawley rats were exposed to toluene (0, 8000, or 12,000 ppm) for 15 min twice daily from postnatal day 28 (P28) through P34 and then euthanized either 1 or 7 days later (on P35 or P42) to assess glutamate (GLU), glutamine, and GABA levels in intact tissue punches from the medial prefrontal cortex (mPFC), anterior striatum and hippocampus. In the mPFC, toluene reduced GLU 1 day after exposure, with no effect on GABA, while after 7 days, GLU was no longer affected but there was an increase in GABA levels. In the hippocampus, neither GABA nor GLU was altered 1 day after exposure, whereas 7 days after exposure, increases were observed in GABA and GLU. Striatal GLU and GABA levels measured after either 1 or 7 days were not altered after toluene exposure. These findings show that 1 week of binge toluene inhalation selectively alters these neurotransmitters in the mPFC and hippocampus in adolescent rats, and that some of these effects endure at least 1 week after the exposure. The results suggest that age-dependent, differential neurochemical responses to toluene may contribute to the unique behavioral patterns associated with drug abuse among older children and young teens.

Just say "I don't": lack of concordance between teen report and biological measures of drug use.

BACKGROUND: Prevalence estimates of illicit drug use by teens are typically generated from confidential or anonymous self-report. While data comparing teen self-report with biological measures are limited, adult studies identify varying degrees of under-reporting. METHODS: Hair analyses for cocaine, opiates and marijuana were compared to confidential teen self- and parent-reported teen drug use in a longitudinal cohort of >400 high-risk urban teens and parents. RESULTS: Both teens and parents substantially underreported recent teen cocaine and opiate use. However, compared with parents, teens were more likely to deny biomarker-verified cocaine use. Teen specimens (hair) were 52 times more likely to identify cocaine use compared with self-report. Parent hair analyses for cocaine and opiate use were 6.5 times and 5.5 times, respectively, more likely to indicate drug use than were parental self-report. The lack of concordance between self-report and bioassay occurred despite participant's knowledge that a "certificate of confidentiality" protected both teen and adult participants, and that the biological specimens would be tested for drugs. CONCLUSIONS: These findings confirm prior reports of adult under-reporting of their own drug use while extending our understanding of teen's self-admitted drug use. The lack of concordance between teen self- or parent-reported teen drug use and biomarkers confirm our concerns that both teen- and parent-reported teen drug use is limited, at least for youth in high-risk urban settings. Methods of ascertainment other than self- or parent-report must be considered when health care providers, researchers and public health agencies attempt to estimate teen drug-use prevalence.

The impact of maternal age on the effects of prenatal alcohol exposure on attention.

BACKGROUND: Prenatal exposure to alcohol has a variety of morphologic and neurobehavioral consequences, yet more than 10% of women continue to drink during pregnancy, placing their offspring at risk for fetal alcohol spectrum disorders (FASD). Identification of at-risk pregnancies has been difficult, in part, because the presence and severity of FASD are influenced by factors beyond the pattern of alcohol consumption. Establishing maternal characteristics, such as maternal age, that increase the risk of FASD is critical for targeted pregnancy intervention. METHODS: We examined the moderating effect of maternal age on measures of attention in 462 children from a longitudinal cohort born to women with known alcohol consumption levels (absolute ounces of alcohol per day at conception) who were recruited during pregnancy. Analyses examined the impact of binge drinking, as average ounces of absolute alcohol per drinking day. Smoking and use of cocaine, marijuana, and opiates were also assessed. At 7 years of age, the children completed the Continuous Performance Test, and their teachers completed the Achenbach Teacher Report Form. RESULTS: After controlling for covariates, stepwise multiple regression analyses revealed a negative relation between levels of prenatal binge drinking and several measures of attention. The interaction between alcohol consumption and maternal age was also significant, indicating that the impact of maternal binge drinking during pregnancy on attention was greater among children born to older drinking mothers. CONCLUSION: These findings are consistent with previous findings that children born to older alcohol-using women have more deleterious effects of prenatal alcohol exposure on other neurobehavioral outcomes.

Differential effects of inhaled toluene on locomotor activity in adolescent and adult rats.

Inhalant abuse is a world-wide public health concern among adolescents. Most preclinical studies have assessed inhalant effects in adult animals leaving unclear how behavioral effects differ in younger animals. We exposed adolescent (postnatal day [PN] 28) and adult (PN90) male rats to toluene using 1 of 3 exposure patterns. These patterns modeled those reported in toluene abuse in teens and varied concentration, number and length of exposures, as well as the inter-exposure interval. Animals were exposed repeatedly over 12 days to toluene concentrations of 0, 8000 or 16,000 parts per million (ppm). Locomotor activity was quantified during toluene exposures and for 30 min following completion of the final daily toluene exposure. For each exposure pattern, there were significant toluene concentration-related increases and decreases in locomotor activity compared to the 0-ppm "air" controls at both ages. These changes depended upon when activity was measured - during or following exposure. Compared to adults, adolescents displayed greater locomotor activity on the first day and generally greater increases in activity over days than adults during toluene exposure. Adults displayed greater locomotor activity than adolescents in the "recovery" period following exposure on the first and subsequent days. Age group differences were clearest following the pattern of paced, brief (5-min) repeated binge exposures. The results suggest that locomotor behavior in rats during and following inhalation of high concentrations of toluene depends on age and the pattern of exposure. The results are consistent with dose-dependent shifts in sensitivity and sensitization or tolerance to repeated toluene in the adolescent animals compared to the adult animals. Alternate interpretations are possible and our interpretation is limited by the range of very high concentrations of toluene used. The results imply that both pharmacological and psychosocial factors contribute to the teen prevalence of inhalant abuse.