Repeated toluene exposure leads to neuroadaptation in dopamine release mechanisms within the nucleus accumbens core.

BACKGROUND: Intentionally inhaling volatile organic solvent like toluene for its intoxicating effects continues to be a public health concern. While repeated abuse of toluene has deleterious behavioral and health effects, little is known about the actions of toluene on the dopaminergic neurotransmitter system within the central nervous system. METHOD: The present study employed complementary neurochemical techniques of slice fast-scan cyclic voltammetry (FSCV) and in vivo microdialysis, to assess dopamine (DA) dynamics immediately after repeated exposure to 2000- or 4000-ppm toluene. DA D3 autoreceptor functionality, measured by FSCV with pharmacological manipulations and brain tissue content analysis with high performance liquid chromatography, were also used to account for the changes in the DA dynamics. RESULTS: Toluene-exposed mice had decreased stimulated DA release only in the nucleus accumbens core immediately after seven days of repeated exposure. DA uptake was decreased in the core only after 2000-ppm exposure. The differences in stimulated DA release were not attributed to alterations in intraneuronal DA levels as measured by tissue content analysis. Basal extracellular DA levels were not significantly different between the air- and toluene-treated mice. However, following an additional toluene exposure, mice had elevated extracellular DA levels in the nucleus accumbens during recovery. This potentiation in extracellular accumbal DA levels was further heightened following potassium stimulation. The accumbal DA D3 autoreceptor function did not appear to play a role as a potential mediator for these differences. CONCLUSION: Our FSCV and microdialysis results suggest a neuroadaptation in DA release mechanics within the nucleus accumbens, but the exact neuronal mechanism of toluene's impact remains elusive.

Lead and cadmium contamination in a large sample of United States infant formulas and baby foods.

Data is limited on lead and cadmium contamination in baby food, a population uniquely susceptible to the toxic effects of heavy metals. The goal of this study was to examine lead and cadmium concentrations in a large convenience sample of US baby foods. We identified the number of baby food product samples that exceeded US FDA and California Proposition 65 limits for daily lead consumption across a range of servings/calories, and the number of samples that exceeded World Health Organization and California Proposition 65 limits for daily cadmium consumption across a range of servings/calories. In total, 564 baby foods were tested across infant and toddler formula, cereals, meals, juices/drinks, jars, pouches, snacks, and electrolyte water. ICP-MS analysis of lead and cadmium was completed using a modified version of EPA method 6020A. Samples were analyzed using kinetic energy distribution mode. Lead was detected in 37% of samples (median = non-detect, 75% = 5.6, maximum = 183.6 µg/kg), and cadmium in 57% (25% = non-detect, median = 2.8, 75% = 9.5, maximum = 103.90 µg/kg). Of 91 infant formula samples, none exceeded FDA lead consumption guidelines in 31 oz, but 22% exceeded the Proposition 65 lead guidelines, 23% exceeded the Proposition 65 cadmium guidelines, and 14% exceeded the WHO tolerable cadmium intake levels for a four-month-old baby. In the solid baby food samples, 1% exceeded FDA lead guidelines in two servings (26% exceeded CA Proposition 65 limits), 3% in 300 cal (34% exceeded CA Proposition 65 limits). For cadmium, 6% exceeded Proposition 65 guidelines in two servings, 8% in 300 cal. There was no association between whether the product was certified organic and its heavy metal concentration. Products containing rice were higher in both lead and cadmium concentrations. Further research is needed to understand the long-term health effects of this chronic daily low level heavy metal exposure in babies.

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.

Toluene's effects on activity and extracellular dopamine in the mouse are altered by GABAA antagonism.

The abuse of inhalants like toluene continues to be widespread around the world, especially among children and teenagers. Despite its frequency of misuse, the dynamics between dopamine (DA) and gamma-aminobutyric acid (GABA) in response to toluene exposure remains unclear. To further decipher toluene's actions, we used a dynamic exposure system in combination with microdialysis to examine in vivo the effects of acutely inhaled toluene on DA release within the mouse caudate putamen (CPu). Results show that toluene inhalation produced increases in DA levels and locomotor activity. In mice that were pretreated with the GABAA antagonist, bicuculline, there was no change in the locomotor response during toluene but activity was potentiated following toluene exposure. Bicuculline pretreatment increased extracellular DA levels during toluene exposure, suggesting that DA and GABA-releasing neuron interaction may play a role in the rewarding properties of toluene.